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Pumilio 2 in neural development, function, and specific neurological disorders

  • Yanchao Lu ORCID logo , Ying Gao ORCID logo , Ranran Chen ORCID logo , Shumin Zhao ORCID logo , Jialing Liu ORCID logo , Sutian Zhang ORCID logo , Xue Bai ORCID logo EMAIL logo and Jingjing Zhang EMAIL logo
Published/Copyright: December 17, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Introduction

Pumilio 2 (PUM2) is an evolutionarily conserved RNA-binding protein that recognizes and binds to the 5′-UGUAXAUA-3′ motif in target mRNAs via its C-terminal domain, thereby reducing mRNA stability and translation efficiency. Recent evidence indicates that PUM2 plays a critical role in nervous system development and function, and its dysregulation contributes to the pathogenesis of certain CNS disorders.

Content

Based on a comprehensive review of existing literature on PUM2and the nervous system in PubMed, this article provides a concise overview of recent advances in understanding the role of the PUM2 protein in central nervous system (CNS) development and disease.

Summary

PUM2 is highly expressed in the central nervous system (CNS), where it regulates nervous system development by participating in neurogenesis and neuronal migration, the differentiation and maturation of neuronal subtypes, and the growth of dendrites and axons. Furthermore, in the mature CNS, PUM2 modulates synaptic types and excitability, regulates the expression of voltage-gated sodium channel proteins, Na+ channel density, neurotransmitter degradation and postsynaptic receptor expression, participates in the regulation of normal nerve signal conduction, and thereby impacts normal nervous system physiology as well as contributing to the pathogenesis of diverse neurological disorders such as epilepsy, stroke, and glioma.

Outlook

This article aims to deepen the understanding of the function of Pumilio2 protein in the nervous system, and hopes to provide new research directions and theoretical support for the treatment strategies of neurological diseases.

Keywords: Pumilio 2; nervous system; dendrites axons; excitability; neurological disorders

Introduction

The Pumilio (Pum) protein family constitutes a class of evolutionarily highly conserved RNA-binding proteins (RBPs) that regulate protein translation and expression by recognizing and binding target nucleic acids via conserved Pumilio homology domains [1]. Genome-wide studies have identified over 4,000 mammalian mRNAs subject to direct or indirect regulation by this family. Pum protein was first discovered in fruit flies and Caenorhabditis elegans, where they play critical roles in embryonic development and germ cell formation [2]. Unlike other RNA families with hundreds of members, the Pum protein family comprises only two members, PUM1 and PUM2, which are highly homologous and are important for maintaining genomic integrity.

In mammals, PUM2 is expressed in multiple organ systems including nervous, cardiovascular, digestive, musculoskeletal, hematopoietic, and reproductive systems, but exhibits highest levels in the brain and testes, where it is involved in the growth, development, and maintenance of these systems. Both PUM2 and PUM1 proteins bind thousands of mRNAs, specifically including at least 694 target genes implicated in axonal guidance, synaptic plasticity, and neurotrophic signaling pathways [3], pathological alterations in these pathways are strongly associated with neurological disorders [4]. Experimentally, silencing PUM2 and PUM1 significantly reduced the number of neural stem cells in the postnatal hippocampus dentate gyrus, increased perinatal cell apoptosis, changed the composition of dentate gyrus cells, and impaired learning and memory ability. This article provides a brief review of recent advances in the role of the PUM2 protein in central nervous system (CNS) development and disease.

Literature search and screening

Studies included in this review were required to meet three criteria [1]: original research elucidating PUM2’s molecular mechanisms [2]; employment of CNS-relevant in vivo or in vitro models [3]; English-language publications with complete datasets. Letters to the editor and articles lacking comprehensive research data were excluded. Primary literature searches were conducted through PubMed using the Boolean query: (Pumilio2 OR PUM2 OR “Pumilio homolog 2”) AND (“central nervous system” OR CNS OR neurodevelopment OR “neurological disorders” OR pathogenesis). All retrieved records were imported into ​EndNote 20​ for deduplication and management. Following initial title/abstract screening against inclusion criteria, full-texts of candidate studies underwent secondary evaluation. Relevant data regarding PUM2’s functions in neural development and pathogenesis were systematically extracted.

The molecular structure and function of PUM2

PUM2 is a∼114 kDa protein encoded by the PUM2 gene, which spans >80 kb across 20 exons on chromosome 2p23-24. This evolutionarily conserved protein is ubiquitously expressed across eukaryotes – from yeast to mammals and plants. PUM2 protein exhibits high evolutionary conservation across species, reflected in its structurally conserved domains. The C-terminus invariably contains a 361-amino acid Pumilio homology domain (PUM-HD) comprising eight tandem imperfect repeats of 36 residues each. Each repeat folds into three α-helices – two elongated helices flanking a shorter central helix – that collectively form a crescent-shaped RNA-binding scaffold. These repeats stack through hydrophobic interfaces to establish the canonical PUM-HD tertiary structure, enabling sequence-specific RNA recognition [5]. Critically, each repeat unit engages in nucleotide-specific interactions with a cognate base within the 8-nt Pumilio-binding element (5′-UGUAXAUA-3′), collectively enabling high-affinity mRNA binding that drives translational repression [6]. The N-terminal domain of PUM2 protein constitutes a low-complexity, intrinsically disordered region enriched in serine, glutamine, and alanine residues. This phylogenetically conserved module shows no significant homology to other known protein domains [7]. Three conserved repressor domains (RDs) within the N-terminal low-complexity region mediate mRNA expression downregulation, though their precise mechanistic basis remains unresolved [8](Figure 1). The crystal structure of PUM2 reveals 292 distinct RNA-binding interfaces, underpinning its capacity to regulate thousands of distinct mRNAs within the nervous system [9]. As an RNA-binding protein, PUM2 could mediate post-transcriptional repression of transcripts through various mechanisms. For example, it could directly recruit CCR4-POP2-NOT (an exonuclease) to function, leading to translational inhibition and mRNA degradation [10]; it could promote the accessibility of miRNAs and thereby trigger repression that is independent of deadenylation; it could also specifically recognize and bind mRNAs containing PBE through its C-terminal Pumilio homology domain, reducing their translation speed and efficiency [11]. Additionally, PUM2 protein plays important roles in many other aspects beyond post-transcriptional regulation, such as suppressing gene programs necessary for maintaining genomic stability, regulating cellular cytosolic sensing of virus infection, and promoting the proliferation of stem cells [12].

PUM2 is involved in the development of the nervous system

The vertebrate nervous system, comprising the central (CNS) and peripheral (PNS) divisions, arises from embryonic ectoderm through neural tube closure and neural crest delamination. The human CNS undergoes four cardinal developmental processes: neural progenitor generation, neuronal migration, synaptogenesis, and myelination during embryogenesis and postnatal maturation [13]. PUM2 protein regulates central nervous system (CNS) development by orchestrating neurogenesis and synaptogenesis (Figure 2).

PUM2 regulates neural development and migration

Neurogenesis is a comprehensive process, encompassing the proliferation of neural stem cells and their balanced and unbalanced divisions to become committed progenitor cells, the gradual migration to functional regions, continuous plastic changes, and the establishment of synaptic connections with other neurons to generate neural functions. During this process, the PUM2 protein promotes the generation and differentiation of neurons, thereby driving the process of neurogenesis. Firstly, during the embryonic development stage, the PUM2 protein facilitates the transformation of embryonic stem cells into neural precursor cells, thereby promoting the development of neurons [14]. Secondly, during the neuronal differentiation stage, the radial glial precursor cells (RPs), which are the precursors of various types of neurons and glial cells in the central nervous system, can directly or indirectly promote the proliferation of intermediate progenitor cells, thereby differentiating into new neurons. The newly formed neurons then migrate to the basal layer of the cortex, forming the new cortical layer. Based on their differentiation sequence, they further construct the deep and shallow layers of the cortex [15]. In this process, the PUM2 protein can bind to the 4E transporter (4E-T) and co-bind to the neural stem cell-specific genes Brn1 and Tle4 mRNA, thereby affecting the translation of these two genes. When PUM2 was knocked down, the Tle4 protein level in Brn1 positive neurons was significantly increased, especially in cortical neurons, causing abnormal co-expression of different neuron-specific proteins. Therefore, in neural development, the PUM2 protein inhibits the production of specific proteins in different regions and neurons to ensure the temporal and spatial specificity of protein production in various sub-neurons, thereby preventing the abnormal co-expression of specific proteins between different cortical neurons [16]. Furthermore, the PUM2 protein can also form an RNA complex with the RNA-binding protein Staufen2 (Stau2). By directly regulating the subcellular localization and potential expression levels of target mRNAs in mammalian neural stem cells, it plays a regulatory role in the self-maintenance and differentiation processes of stem cells [17]. When PUM2 and STAU2 are functionally knocked down, the complex is disrupted, causing the radial glial progenitor cells to differentiate into neurons prematurely, leading to incorrect localization and expression of their target mRNAs. These results suggest that the PUM2 protein plays a stable and protective role in the normal differentiation and localization of neural cells.

PUM2 orchestrates neural development and migration precision

PUM2 protein further specifies neuronal identity determinants critical for subtype differentiation. The neocortex is the largest and most complex structure in the mammalian brain. It is located at the top layer of the cerebral hemispheres and is about 2–4 mm thick. It is divided into four planar regions and six spatial levels and plays a crucial role in processing sensory information, controlling movement, and advanced cognition [18]. Functionally distinct regions contain heterogeneous populations of neurons characterized by their morphology, connectivity, molecular code, and function. However, how do neurons in different regions connect, and how are subtypes distinguished? A study found that Pum2 knockdown significantly increased the density of SOX5+/BCL11B+ neurons in the V layer of the anterior parietal and prefrontal cortex [19], In contrast, Rorβ+ neurons density in layer IV decreased under the same condition. To determine whether these alterations stemmed from changes in neuronal density, migration defects, or phenotypic reprogramming, the authors performed DAPI staining on layers IV and V in both Pum2-knockdown and control groups. Quantitative analysis revealed unchanged total neuronal counts in these layers, but significant shifts in neuronal subtype proportions. Therefore, the authors hypothesized that PUM2 protein did not affect the number of cells but caused changes in the neuron identity determinant on the surface of neurons. Collectively, these data establish PUM2’s essential role in specifying neuronal identity determinants during cortical development.

PUM2 protein is also important for the maturation of neurons. PUM2 and PUM1 protein could work together to promote the division and differentiation of neural stem cells, which has been confirmed in some studies. In a pivotal study [3], neural stem cells (NSCs) with concomitant Pum1/Pum2 double-knockout (dKO) were compared to wild-type (WT) controls. Primary neurospheres (>30 μm diameter) were quantified at day 7 post-culture, dKO NSPCs formed much fewer and much smaller primary neurospheres compared with controls cells, but they also had lower self-renewing division. These data demonstrate that PUM2 protein deficiency critically compromises NSC self-renewal and differentiation capacity. To isolate Pum2-specific functions, mature cortical neurons were transduced with a shRNA construct targeting Pum2 (shPum2) using lentiviral vectors [20], after confirming that the lentivirus could specifically knock down Pum2, the researchers found that the surface area of the somatic cells with Pum2 knockdown decreased, indicating that the reduction of PUM2 protein would impair neuronal development and maturation. Collectively, these studies establish that PUM2 orchestrates neuronal growth, maturation, and molecular identity specification. However, current evidence derives exclusively from in vitro and animal models, lacking validation in human-derived systems (e.g., iPSC-derived neurons or postmortem tissue). Moreover, the mechanistic underpinnings – particularly spatiotemporally resolved RNA-protein interactomes and ​downstream signaling flux – demand multimodal dissection integrating live-cell imaging, ribonomics, and functional validation.

PUM2 adjusts dendritic and axonal morphogenesis

In neurons, axonal development including growth, branching, target innervation, and functional maintenance critically depends on localized protein synthesis. This process initiates when neuronal mRNAs assemble with ribonucleoprotein particles (RNPs) to form transport-competent complexes. These mRNA-RNP complexes are then actively trafficked along microtubules to subcellular compartments such as axons or dendrites for spatiotemporally precise translation. PUM2 protein exhibits strict somatic enrichment in developing neurons, spatially restricting target mRNA localization through sequence-specific binding. By recognizing PBEs, PUM2 protein retains transcripts in the soma, thereby preventing their axonal transport and subsequent translation [3]. Among them, glycogen synthase kinase 3β (Gsk3β) and cell adhesion molecule (L1cam) are both target mRNAs of PUM2 protein [21], PUM2 protein recognizes both transcripts via its PUM-HD domain and represses their translation during local protein synthesis in axons. Gsk3β is a serine/threonine kinase expressed in axons, which regulates axonal growth through phosphorylating various proteins. For example, it phosphorylates microtubule-associated proteins, leading to decreased stability of microtubules and inhibition of axon elongation [22]. Concurrently, Gsk3β regulates the activity of actin, causing disruption of the polymerization-depolymerization balance of actin, leading to inhibition of axon elongation. L1cam is a transmembrane glycoprotein that mediates contact-dependent signaling through physical interaction with Robo receptors. This ligand-receptor complex orchestrates neurite fasciculation by coordinating F-actin dynamics within growth cones, enabling precise guidance of both axonal and dendritic processes [23], Pum2-deficient neurons exhibited axonal growth and branching defects in vivo, and impaired axon regeneration in vitro [21]. Collectively, in vivo and vitro evidence establishes. PUM2 protein as a critical regulator of axonal growth, development, and repair. While current data indicate PUM2 protein modulates axonal protein synthesis through mRNA transport regulation, direct experimental verification via coordinated manipulation of PUM2 protein and its effector proteins remains lacking. Furthermore, although phenotypic studies demonstrate PUM2’s roles in axonal morphogenesis and regeneration, the underlying spatiotemporal mechanisms require deeper mechanistic dissection.

Additionally, PUM2 protein also plays an important regulatory role in the growth and development of neuronal dendrites. It has also been reported that PUM2 protein is more abundant in dendrites than in axons, with prominent localization to dendritic spines. These PUM2 proteins can bind to eukaryotic initiation factor 1A (EIF1A) and eukaryotic initiation factor 4E (EIF4E) in dendrites [24]. During translation initiation, EIF1A can bind to the 40S ribosome during translation initiation, accelerating the ribosome’s start codon recognition and promoting mRNA expression. EIF4E can bind to the 5′ cap structure of mRNA during translation and recruit the small subunit of the ribosome and other translation initiation factors to form a translation complex, by suppressing EIF1A and EIF4E within dendritic spines, PUM2 protein regulates dendritic morphogenesis through localized translational control [25]. PUM2 protein can reduce dendritic spines and increase dendritic arborization in mature neurons, and increase dendritic spines and dendritic arborization in immature neurons [26]. Another study also showed that the knockout of the Pum2 gene could lead to an increase in the number of short dendrites in mature hippocampus neurons [27]. The increased dendritic branching of hippocampal neurons resulting from PUM2 deficiency has also been confirmed in Pum2 −/− mice [28], pyramidal cells in the CA1 layer of the hippocampus showed a significant increase in primary dendritic branches and a marked increase in synaptic density at the tips of their dendrites in Pum2 −/− mice Furthermore, the length and width of the postsynaptic density projection were higher than those of WT mice. While PUM2 protein exhibits distinct, stage-specific functions in mature vs. immature neurons, ​the above findings from cellular and in vivo models have proposed its bidirectional regulatory role in dendritic morphogenesis. However, the molecular determinants underlying this context-dependent duality – particularly the temporal switch in RNA-binding specificity and downstream signaling cascades – remain incompletely characterized. Elucidating how PUM2’s regulatory logic adapts across neurodevelopmental epochs represents a critical knowledge gap.

PUM2 modulates neural excitability

Neural conduction is an electrical and chemical sequence of events that occurs along nerve fibres and plays an important role in transmitting information, coordinating body movements, responding to external stimuli, and maintaining the function of the nervous system. However, neurons do not connect directly to each other, they communicate through synaptic structures. A complete synaptic structure includes the presynaptic membrane, the synaptic cleft, and the postsynaptic membrane, which are an asymmetric intercellular connection that can mediate rapid point-to-point communication between neurons, connect neurons to circuits, and process information during transmission [29]. PUM2 protein may be involved in the normal regulation of nerve signaling through the structure and function of synapses, the expression of sodium channels, and other aspects that influence the normal physiological function of the nervous system and the onset of disease.

PUM2 regulates synaptic excitability

Synapses are the key connection structures that enable information transmission between neurons and effector cells. Studies have shown that the PUM2 protein plays a significant role in regulating the formation of synapses, influencing the type, density, and maturation status of these structures. The deficiency of PUM2 results in a higher prevalence of asymmetric synapses and enhances synaptic transmission at excitatory synapses. It also increases both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs), while reducing the amplitude of postsynaptic currents at inhibitory synapses. These changes collectively lead to an overall increase in neuronal excitability [26], 28], 30]. In addition, the PUM2 protein also affects synapse function. First, PUM2 protein affects the levels of several key regulators of GABAergic neurotransmitters, such as porphyrins, vesicular inhibitory amino acid transporter protein (Vgat), sodium and chloride-dependent GABA transporter protein 1 (Gat1), glutamate decarboxylase 1 (Gad1) and somatostatin (SST), and subsequently affects the function of GABAergic synapses [31]. A proteomics study showed that these regulators associated with GABAergic synapses were reduced explicitly in neurons after Pum2 knockout, and a reduction in the amplitude of small inhibitory postsynaptic currents (mPIPSCs) was detected in GABAergic neurons, but not in inhibitory presynaptic currents (IPSCs) or spontaneous postsynaptic currents [28]. Moreover, PUM2 protein enhances the expression of multiple excitatory synaptic proteins, notably upregulating the AMPA receptor subunit GluA2 (formerly GLUR2) in temporal lobe circuits, thereby potentiating glutamatergic transmission and increasing regional neuronal excitability. PUM2 protein can also modulate the concentration of acetylcholine in the synaptic cleft by affecting acetylcholinesterase (AChE), which in turn affects synaptic function. Previous studies have demonstrated that PUM2 protein specifically recognizes and binds to the 3′ untranslated region (3′-UTR) of AChE mRNA, thereby suppressing its translational activity. This post-transcriptional regulation leads to a significant reduction in acetylcholinesterase abundance within the synaptic cleft, ultimately impairing cholinergic neurotransmission by disrupting the physiological degradation of acetylcholine at synaptic junctions [32]. These findings demonstrate that PUM2 protein can influence synaptic excitability by affecting synapse types, synaptic regulators and the levels of pre- and postsynaptic currents.

PUM2 affects the expression of voltage-gated sodium channel proteins, leading to epilepsy susceptibility

Voltage-gated sodium channels are heteromeric transmembrane glycoprotein complexes localized on plasma membranes, comprising pore-forming α subunits and regulatory β subunits. These macromolecular assemblies serve as fundamental molecular determinants for the rapid initiation and propagation of action potentials through voltage-dependent conformational changes, thereby establishing essential electrochemical gradients that govern neuronal excitability and signal transduction in excitable tissues. The genes encoding sodium channels are evolutionarily highly conserved, and the α-subunit (Nav) family in the human genome comprises 10 genes, of which the genes SCN1A, SCN2A, and SCN8A encoding Nav1.1, Nav1.2, and Nav1.6 are highly expressed in neurons in the CNS [33]. The PUM2 protein could regulate the density of sodium channels by binding to the mRNA transcripts of SCN1A, SCN2A, and SCN8A, thereby inhibiting the normal translation processes of Nav1.1, Nav1.2, and Nav1.6 [34]. In the CNS, voltage-gated sodium channels are involved in the firing processes of neurons, and their abnormal expression is often the cause of epilepsy [35]. Nav1.1, encoded by SCN1A, is mainly distributed in GABAergic neurons in the nervous system, and its expression is closely related to the activity of GABAergic neurons. Abnormal expression of it will interfere with the activity of GABAergic neurons, affecting the balance of excitation and inhibition in the nervous system, and thus leading to epilepsy [36]. Nav1.2, encoded by SCN2A, is mainly located in excitatory neurons in the nervous system, and its expression level is related to the maturation and distribution of GABAergic neurons, playing an important role in the function of inhibitory neuronal networks [37]. Nav1.6, encoded by SCN8A, is mainly located at the excitatory axon terminals. An increase in its expression will cause excitatory neurons to be more prone to generating action potentials and increase the discharge frequency, which disrupts the balance of excitation and inhibition in the brain and leads to excessive excitation of neurons [38]. Experimental investigations demonstrated that Pum2-deficient mice exhibit a heightened susceptibility to spontaneous paroxysmal epileptiform activity. Mechanistic analyses through quantitative immunohistochemical analyses of hippocampal dorsal coronal sections (CA1 stratum pyramidale) revealed dysregulated sodium channel homeostasis, characterized by upregulated Nav1.1 (SCN1A) and Nav1.2 (SCN2A) isoforms juxtaposed with diminished Nav1.6 (SCN8A) expression. These alterations in voltage-gated sodium channel subtypes suggest a pathophysiological mechanism by which PUM2-mediated post-transcriptional regulation modulates neuronal hyperexcitability through coordinated regulation of Nav subunit stoichiometry in the nervous system [39].

PUM2 deficiency is associated with epilepsy

Epilepsy is a common neurological disorder that affects people worldwide, characterised by clinical features of excessive and hypersynchronous neuronal discharges in the brain network. Under normal circumstances, the discharges between neurons are orderly and coordinated. However, in epilepsy patients, due to the disruption of the stability of the neuronal membrane, neurons become overly excited and generate abnormal electrical signals, which eventually trigger epileptic seizures [40]. Various underlying etiologies, including genetic susceptibility, structural abnormalities, metabolic disorders, and acquired brain injuries, cause this episodic disorder. Abnormal ion channel function is also an important factor in the pathogenesis of epilepsy. Ion channels are crucial regulators of the ion balance inside and outside neurons and play a key role in neuronal excitation and inhibition [41]. Some gene mutations or drug-induced ion channel abnormalities may lead to excessive neuronal excitation in the brain, thereby triggering epileptic seizures. Such abnormalities may include excessive opening or insufficient closure of ion channels, resulting in an imbalance of ion concentrations within neurons. As a chronic neurological disorder with severe comorbidities, epilepsy imposes a heavy burden on the public health system. It affects individuals and their families, including direct medical costs, social and psychological consequences, and an increased risk of death.

PUM2 is expressed in various regions of the cerebral cortex, amygdala, thalamus, hypothalamus and cerebellum, with the highest expression in the temporal lobe, and immunohistochemical staining of temporal cortex samples from patients with temporal lobe refractory epilepsy revealed significantly lower levels of PUM2 protein [30]. Further animal studies have also confirmed that Pum2 deficiency results in spontaneous EEG abnormalities and lower seizure thresholds in mice [39]. The possible mechanisms are as follows: first, the expression of hundreds of mRNAs in the brain is upregulated in Pum2 deficiency, and some of them are involved in the regulation of synaptic structure and excitability. In addition, PUM2 protein could regulate the expression levels of Nav1.1, Nav1.2, and Nav1.6 in the nervous system, where these sodium ion channels play an important role in epileptic seizures [42], 43]. As mentioned in the above content, the expression changes of these three sodium ion channels will affect the balance of excitation and inhibition in the brain, leading to excessive excitability of the nervous system and thus causing epilepsy. PUM2 protein has also been demonstrated to regulate several proteins associated with excitatory synaptic function, including GluA2. A reduction in PUM2 protein has been observed to increase GluA2 expression and neuronal excitation [28]. Consequently, the utilization of PUM2 protein as a therapeutic target to modulate sodium channel protein and neurotransmitter expression may prove efficacious in the amelioration of abnormal neuronal firing, thus providing a novel approach to the treatment of epilepsy.

PUM2 participates in neuronal injury after stroke

Stroke is the second leading cause of death and the third leading cause of disability globally. Its subtypes are distributed as follows: 62 % are ischemic strokes, 28 % are hemorrhagic strokes, and 10 % are subarachnoid haemorrhages. Both ischemic and hemorrhagic strokes can inflict damage on brain tissue, yet the mechanisms underlying the brain injury they trigger are distinct. In ischemic stroke, the primary causes of brain tissue damage encompass energy supply disruptions, excitotoxicity, oxidative stress, and inflammatory responses. For hemorrhagic stroke, the main mechanisms involve the space-occupying effect of the hematoma, the toxic effects of blood components, cerebral oedema, and elevated intracranial pressure. Moreover, regardless of whether an ischemic or hemorrhagic stroke occurs, it activates the immune system. This prompts peripheral immune cells to migrate to the perivascular space and brain parenchyma. These immune cells that infiltrate the brain release a substantial amount of proteases, reactive oxygen and nitrogen species, and inflammatory cytokines. This subsequently leads to nerve damage, thereby exacerbating neuroinflammation and neurovascular damage [44]. Consequently, regulating the levels of the inflammatory response and oxidative stress significantly influences the reduction of nerve damage and subsequent recovery. However, the PUM2 protein plays different regulatory roles in these two types of strokes.

Some animal and in vitro studies have shown that cerebral ischemia or hypoxia-glucose deprivation can lead to increased expression of PUM2. Further research has shown that high levels of PUM2 protein exacerbate I/R-induced neuroinflammation and brain damage. Sirtuin type 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, a member of the sirtuin family, which is closely associated with cell proliferation, differentiation, senescence, apoptosis, and metabolism. When ischemia-reperfusion occurs, SIRT1 is highly expressed to help restore mitochondrial homeostasis, regulate oxidative stress and inflammatory responses, and inhibit neuronal apoptosis, thereby protecting brain tissue from I/R injury. PUM2 protein could reduce the stability of SIRT1 and decrease its expression, leading to a decrease in the expression of SLC7A11, an increase in ferroptosis and neuroinflammation, and an exacerbation of cerebral ischemia/reperfusion injury [45]. However, one study found that PUM2 protein was significantly lower in the early stages of subarachnoid hemorrhage animal models compared to controls, but increased in the later stages and that overexpression of PUM2 protein can reduce oxidative stress and neuronal death, thereby improving behavior and cognitive function in SAH animal models [46]. These results indicate that PUM2 protein plays a regulatory role in the prognosis of stroke and neuronal apoptosis. However, the role of the PUM2 protein in ischemic stroke and hemorrhagic stroke is opposite. This may be due to the different pathogenesis of these two diseases and the different pathways of oxidative stress and inflammatory responses they trigger, so their role may be different or even opposite.

PUM2 May inhibit vasculogenic mimicry of glioma

Glioma is the most common primary tumour in the brain and spinal cord. From a histological perspective, they can originate from normal glial cells, glial precursor cells, stem cells, and other cell types. Gliomas mainly include astrocytoma, oligodendroglioma, oligoastrocytoma, ependymoma, and neuronal and mixed neuronal-glial tumours. According to their degree of malignancy, they can be further classified into grade I pilocytic astrocytoma, pleomorphic xanthoastrocytoma and subependymal giant cell astrocytoma, grade II oligodendroglioma and astrocytoma, grade III anaplastic oligodendroglioma, anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic ependymoma, and grade IV glioblastoma (GBM) [47]. The symptoms of glioma are diverse and vary depending on the site of origin, which can manifest as focal neurological deficits, encephalopathy or seizures. The aetiology and pathogenesis of glioma remain unclear, but high-dose ionising radiation and high-index gene mutations associated with rare syndromes are important risk factors. More than half of gliomas are glioblastomas. The average survival time of patients is about 15 months, and the 5-year survival rate is less than 7 % [48].

Vasculogenic mimicry (VM) is an endothelium-independent tumor microcirculation pattern manifested by tumor cells with “endothelial cell function” through their deformation and stromal remodeling to form pipeline structures, with erythrocytes visible inside the pipeline, capable of providing sufficient blood supply for tumor growth, and is closely related to tumor grading, invasion, metastasis, and poor prognosis [49]. Recent work identifies SUMOylation of PUM2 protein as the critical initiator of the PUM2-CEBPD-DSG2 axis, driving VM in gliomas [50]. Elevated expression of ubiquitin-conjugating enzyme E2I (UBE2I) during gliomagenesis promotes PUM2 protein SUMOylation in tumor tissues and cell. SUMOylation of PUM2 protein not only reduces the stability of the PUM2 protein but also weakens the inhibitory effect of PUM2 protein on CCAAT enhancer-binding protein δ (CEBPD) mRNA, thereby increasing CEBPD expression. CEBPD is a b-ZIP transcription factor that can bind to the DNA regulatory region to promote transcription, and the upregulated CEBPD facilitates binding to the upstream promoter region of the calcium-dependent desmosomal cadherin (DSG2) gene and upregulates DSG2 expression, which induces VM development in glioma. The abnormal expression of heme oxygenase-1 (HO-1) is closely related to the occurrence or progression of various tumours, including bladder cancer, breast cancer, colon cancer and glioma [51]. Analysis of the GSE4412 microarray dataset revealed an inverse correlation between PUM2 and HO-1 expression in grade IV gliomas. Complementary in vitro cellular assays demonstrated that HO-1 promotes proliferative clonality in glioma cell lines (A172 and U87-MG) [52]. However, this study did not extend to functional validation of PUM2 protein across glioma grades or elucidate its mechanistic role in tumour progression. We propose that this apparent contradiction is resolved by disease stage specificity: PUM2 protein degradation promotes VM in advanced tumour, while PUM2 protein suppression enables HO-1-driven proliferation in glioblastoma. Critically, neither study mechanistically links HO-1 to PUM2 protein SUMOylation or tests functional crosstalk between the VM and proliferation pathways. However, the findings on the role of PUM2 protein in the proliferation of gliomas are not consistent. Recent studies have shown that the expression of PUM2 is increased in glioblastoma tumor tissue and cell lines. It has been shown to promote glioblastoma proliferation and migration by inhibiting the expression of the cell cycle regulator BTG1. Using shRNA to reduce the expression of the PUM2 protein can significantly inhibit the proliferation of glioblastoma cells while suppressing cell migration and invasion [53]. The opposing roles of PUM2 in glioma may be due to the experimental methods and cell types adopted in the research. The previous study selected human glioma tissues and human glioma cell lines (U251, U373) as research materials, and used a three-dimensional culture method to observe their angiogenesis simulation ability. The approach could more realistically reflect the growth characteristics of tumors in the human body. In contrast, the latter study maintained glioblastoma cell lines (U-87MG, T98G, U-251MG, and A172) in ​monolayer culture​ under standard adherent conditions, which possibly ignoring the potential influence of PUM2 protein on angiogenesis simulation. The definitive mechanisms by which PUM2 regulates glioma proliferation and metastatic potential require further elucidation through advanced in vivo models and patient-derived organoid studies.

Conclusions

As an RNA-binding protein, PUM2 protein is highly expressed in the nervous system, where it plays a pivotal role in neuronal development and electrical signaling. PUM2 protein regulates these processes by binding to and inhibiting the translation of hundreds to thousands of target mRNAs, thereby maintaining the normal physiological functions of the nervous system. However, dysregulation of PUM2 expression has been implicated in increasing susceptibility to or exacerbating the severity of various neurological disorders, including epilepsy, stroke, and glioma. Therefore, the development of drugs targeting PUM2 is of great significance in the treatment of specific neurological disorders. However, like other RBPs, the research on PUM2 protein as a therapeutic strategy for diseases is still in its infancy and progressing relatively slowly. This is because they play a pivotal role in the gene regulatory network, making it extremely difficult to predict the downstream effects of RNA-binding protein therapies. Some studies have used materials such as polyethyleneimine (PEI), glutathione (GSH), and mesoporous silica nanoparticles (MSN) to encapsulate anti-Pum2 siRNA to form nanoparticles [54], in animal models, the expression of Pum2 is intervened through intravenous injection to treat colorectal cancer. However, enabling the drug to pass through the physiological barriers in the body and accurately reach the designated site of action, as well as achieve precise targeted treatment of diseases and reduce side effects, remains a major challenge, further in-depth studies into the molecular mechanisms of PUM2 protein in these contexts are essential.

Figure 1: Structural and functional architecture of Pum1/2 repression machinery. PUM2 is a 114 kDa protein encoded by a gene with 20 exons. At the C-terminus, PUM2 contains a typical Pumilio homology domain (HD) that recognizes and binds to mRNA containing the 5′-UGUAXAUA-3′ Pumilio binding element (PBE) to repress its translation. At the N-terminus, PUM2 has three RD inhibitory domains that could reduce the expression level of the target mRNA (Schematics were created using [Figdraw] and are licensed under a paid subscription. All elements were designed de novo by the authors based on established molecular mechanisms).
Figure 1:

Structural and functional architecture of Pum1/2 repression machinery. PUM2 is a 114 kDa protein encoded by a gene with 20 exons. At the C-terminus, PUM2 contains a typical Pumilio homology domain (HD) that recognizes and binds to mRNA containing the 5′-UGUAXAUA-3′ Pumilio binding element (PBE) to repress its translation. At the N-terminus, PUM2 has three RD inhibitory domains that could reduce the expression level of the target mRNA (Schematics were created using [Figdraw] and are licensed under a paid subscription. All elements were designed de novo by the authors based on established molecular mechanisms).

Figure 2: PUM2 regulatory network in neuronal development. In the normal state, PUM2 suppresses the expression of EIF1A and EIF4E and dendritic growth, promotes axonal growth by regulating the expression of glycogen synthase kinase 3β (Gsk3ß) and cell adhesion molecule (Llcam) within axons, and controls synaptic function by downregulating the expression of synaptic-related proteins and Nav1.1 and Nav1.3 channels while upregulating the expression of Nav1.6. The above results are reversed in the absence of PUM2 (Schematics were created using [Figdraw] and are licensed under a paid subscription. All elements were designed de novo by the authors based on established molecular mechanisms).
Figure 2:

PUM2 regulatory network in neuronal development. In the normal state, PUM2 suppresses the expression of EIF1A and EIF4E and dendritic growth, promotes axonal growth by regulating the expression of glycogen synthase kinase 3β (Gsk3ß) and cell adhesion molecule (Llcam) within axons, and controls synaptic function by downregulating the expression of synaptic-related proteins and Nav1.1 and Nav1.3 channels while upregulating the expression of Nav1.6. The above results are reversed in the absence of PUM2 (Schematics were created using [Figdraw] and are licensed under a paid subscription. All elements were designed de novo by the authors based on established molecular mechanisms).

Corresponding authors: Xue Bai and Jingjing Zhang, Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng Clinical Medical College of Inner Mongolia Medical University, Hada Sub-district, Hongshan District, Chifeng City, Inner Mongolia, 224000, P.R. China, E-mail: (X. Bai), (J. Zhang).
Xue Bai and Jingjing Zhang share senior authorship. The idea for this review topic was conceived by Xue Bai and Jingjing Zhang, who also contributed to revising the manuscript. Yanchao Lu, as the first author, was responsible for designing and writing the manuscript as well as drawing the charts. Ying Gao, Ranran Chen, Shumin Zhao, Jiangling Liu, and Sutian Zhang took part in the article writing discussion and were involved in drafting and modifying the figure. All authors made contributions to revising the manuscript and approved the submitted version.

  1. Funding information: This work was supported by the National Natural Science Foundation of China (82160320), the Central Government Guides Local Science and Technology Development Fund Projects (2021ZY0010), Science and Technology Programof the Joint Fund of Scientific Research for the Public Hospitals of Inner Mongolia Acadcmy of Medical Sciences (2023GLLH0309).

  2. Author contribution: The idea for this review topic was conceived by JJZ and XB, who also contributed to revising the manuscript. CYL was responsible for designing and drafting the manuscript and figures. YG, MSZ, RRC, LJL, and TSZ took part in the article writing discussion and were involved in drafting and modifying the figure. All authors made contributions to revising the manuscript and approved the submitted version.

  3. Conflict of interest: No conflicts of interest.

  4. Data Availability Statement: Not applicable.

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Received: 2025-04-15
Accepted: 2025-10-10
Published Online: 2025-12-17

© 2025 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
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  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
  158. Efficacy and safety of PD-1/PD-L1 inhibitors in pancreatic ductal adenocarcinoma: a systematic review and Meta-analysis of randomized controlled trials
  159. The value of diagnostic experience in O-RADS MRI score for ovarian-adnexal lesions
  160. Health education pathway for individuals with temporary enterostomies using patient journey mapping
  161. Serum TLR8 as a potential diagnostic biomarker of coronary heart disease
  162. Intraoperative temperature management and its effect on surgical outcomes in elderly patients undergoing lichtenstein unilateral inguinal hernia repair
  163. Immunohistochemical profiling and neuroepithelial heterogeneity in immature ovarian teratomas: a retrospective digital pathology-based study
  164. Associated risk factors and prevalence of human papillomavirus infection among females visiting tertiary care hospital: a cross-sectional study from Nepal
  165. Comparative evaluation of various disc elution methods for the detection of colistin-resistant gram-negative bacteria
  166. Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
  167. Causal association between ceramide levels and central precocious puberty: a mendelian randomization study
  168. Novel predictive model for colorectal liver metastases recurrence: a radiomics and clinical data approach
  169. Relationship between resident physicians’ perceived professional value and exposure to violence
  170. Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
  171. Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
  172. Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
  173. Impact of combined diaphragm-lung ultrasound assessment on postoperative respiratory function in patients under general anesthesia recovery
  174. Development and internal validation of a nomogram for predicting short-term prognosis in ICU patients with acute pyelonephritis
  175. The association between hypoxic burden and blood pressure in patients with obstructive sleep apnea
  176. Promotion of asthenozoospermia by C9orf72 through suppression of spermatogonia activity via fructose metabolism and mitophagy
  177. Review Articles
  178. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  179. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  180. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  181. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  182. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  183. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  184. The application of augmented reality in robotic general surgery: A mini-review
  185. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  186. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  187. Plant polyphenols, terpenes, and terpenoids in oral health
  188. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  189. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  190. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  191. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  192. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  193. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  194. Giant borderline ovarian tumours – review of the literature
  195. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  196. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  197. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  198. Supplement strategies for infertility in overweight women: Evidence and legal insights
  199. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  200. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  201. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  202. Strategies for hyperkalemia management in dialysis patients: A systematic review
  203. C-reactive protein-to-albumin ratio in peripheral artery disease
  204. Research progress on autophagy and its roles in sepsis induced organ injury
  205. Neuronutrition in autism spectrum disorders
  206. Pumilio 2 in neural development, function, and specific neurological disorders
  207. Antibiotic prescribing patterns in general dental practice- a scoping review
  208. Clinical and medico-legal reflections on non-invasive prenatal testing
  209. Smartphone use and back pain: a narrative review of postural pathologies
  210. Targeting endothelial oxidative stress in hypertension
  211. Exploring links between acne and metabolic syndrome: a narrative review
  212. Case Reports
  213. Delayed graft function after renal transplantation
  214. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  215. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  216. Giant right atrial hemangioma presenting with ascites: A case report
  217. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  218. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  219. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  220. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  221. Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
  222. A rare case of Opalski syndrome with a suspected multiple sclerosis etiology
  223. Newly diagnosed B-cell acute lymphoblastic leukemia demonstrating localized bone marrow infiltration exclusively in the lower extremities
  224. Rapid Communication
  225. Biological properties of valve materials using RGD and EC
  226. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  227. Repeat influenza incidence across two consecutive influenza seasons
  228. Letter to the Editor
  229. Role of enhanced external counterpulsation in long COVID
  230. Expression of Concern
  231. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  232. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  233. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  234. Corrigendum
  235. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  236. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  237. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  238. Retraction
  239. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  240. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  241. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  242. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  243. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  244. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  245. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  246. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  247. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  248. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  249. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  250. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  251. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  252. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  253. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  254. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  255. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  256. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  257. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  258. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  259. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  260. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  261. A review of brain research on T2DM-related cognitive dysfunction
  262. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  263. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  264. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2025-1332
Keywords for this article
Pumilio 2; nervous system; dendrites axons; excitability; neurological disorders
Creative Commons
BY 4.0

Articles in the same Issue

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  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
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  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
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  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
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  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
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  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
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  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
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  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
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  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
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  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
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  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
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  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
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  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
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  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
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  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
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  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
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  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
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  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
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  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
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  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
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  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
  158. Efficacy and safety of PD-1/PD-L1 inhibitors in pancreatic ductal adenocarcinoma: a systematic review and Meta-analysis of randomized controlled trials
  159. The value of diagnostic experience in O-RADS MRI score for ovarian-adnexal lesions
  160. Health education pathway for individuals with temporary enterostomies using patient journey mapping
  161. Serum TLR8 as a potential diagnostic biomarker of coronary heart disease
  162. Intraoperative temperature management and its effect on surgical outcomes in elderly patients undergoing lichtenstein unilateral inguinal hernia repair
  163. Immunohistochemical profiling and neuroepithelial heterogeneity in immature ovarian teratomas: a retrospective digital pathology-based study
  164. Associated risk factors and prevalence of human papillomavirus infection among females visiting tertiary care hospital: a cross-sectional study from Nepal
  165. Comparative evaluation of various disc elution methods for the detection of colistin-resistant gram-negative bacteria
  166. Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
  167. Causal association between ceramide levels and central precocious puberty: a mendelian randomization study
  168. Novel predictive model for colorectal liver metastases recurrence: a radiomics and clinical data approach
  169. Relationship between resident physicians’ perceived professional value and exposure to violence
  170. Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
  171. Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
  172. Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
  173. Impact of combined diaphragm-lung ultrasound assessment on postoperative respiratory function in patients under general anesthesia recovery
  174. Development and internal validation of a nomogram for predicting short-term prognosis in ICU patients with acute pyelonephritis
  175. The association between hypoxic burden and blood pressure in patients with obstructive sleep apnea
  176. Promotion of asthenozoospermia by C9orf72 through suppression of spermatogonia activity via fructose metabolism and mitophagy
  177. Review Articles
  178. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  179. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  180. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  181. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  182. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  183. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  184. The application of augmented reality in robotic general surgery: A mini-review
  185. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  186. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  187. Plant polyphenols, terpenes, and terpenoids in oral health
  188. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  189. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  190. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  191. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  192. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  193. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  194. Giant borderline ovarian tumours – review of the literature
  195. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  196. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  197. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  198. Supplement strategies for infertility in overweight women: Evidence and legal insights
  199. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  200. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  201. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  202. Strategies for hyperkalemia management in dialysis patients: A systematic review
  203. C-reactive protein-to-albumin ratio in peripheral artery disease
  204. Research progress on autophagy and its roles in sepsis induced organ injury
  205. Neuronutrition in autism spectrum disorders
  206. Pumilio 2 in neural development, function, and specific neurological disorders
  207. Antibiotic prescribing patterns in general dental practice- a scoping review
  208. Clinical and medico-legal reflections on non-invasive prenatal testing
  209. Smartphone use and back pain: a narrative review of postural pathologies
  210. Targeting endothelial oxidative stress in hypertension
  211. Exploring links between acne and metabolic syndrome: a narrative review
  212. Case Reports
  213. Delayed graft function after renal transplantation
  214. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  215. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  216. Giant right atrial hemangioma presenting with ascites: A case report
  217. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  218. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  219. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  220. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  221. Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
  222. A rare case of Opalski syndrome with a suspected multiple sclerosis etiology
  223. Newly diagnosed B-cell acute lymphoblastic leukemia demonstrating localized bone marrow infiltration exclusively in the lower extremities
  224. Rapid Communication
  225. Biological properties of valve materials using RGD and EC
  226. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  227. Repeat influenza incidence across two consecutive influenza seasons
  228. Letter to the Editor
  229. Role of enhanced external counterpulsation in long COVID
  230. Expression of Concern
  231. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  232. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  233. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  234. Corrigendum
  235. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  236. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  237. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  238. Retraction
  239. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  240. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  241. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  242. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  243. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  244. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  245. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  246. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  247. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  248. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  249. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  250. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  251. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  252. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  253. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  254. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  255. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  256. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  257. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  258. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  259. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  260. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  261. A review of brain research on T2DM-related cognitive dysfunction
  262. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  263. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  264. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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