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RNF144A and RNF144B: Important molecules for health

  • Wang Jiang , Yi Liang , Min Han , Wenhua He , Kun Chen , Chongtian Deng and Yueming Shen EMAIL logo
Published/Copyright: August 1, 2025
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From the journal Open Life Sciences Volume 20 Issue 1

Abstract

RNF144 family proteins, including RNF144A and RNF144B, members of the RING-between-RING domain-containing ubiquitin E3 ligase family, serve as critical regulators of protein ubiquitination. Despite increasing research attention in recent years, particularly regarding their distinct functional roles in pathophysiological processes, a comprehensive synthesis of existing findings remains absent. To address this knowledge gap, we conducted a systematic literature search in PubMed using the following query terms: “RNF144,” “RNF144A,” “RNF144B,” “PIR2,” “IBRDC2,” and “P53RFP.” This review systematically examines current evidence regarding the molecular mechanisms and pathophysiological significance of RNF144A/B across various disease systems. Through critical analysis of structural characteristics, substrate interactions, and signaling pathways, we aim to clarify their dual roles in cellular homeostasis and disease pathogenesis. This synthesis not only consolidates current understanding but also identifies key knowledge gaps requiring further investigation, particularly regarding isoform-specific functions and therapeutic targeting potential.

Graphical abstract

Keywords: RNF144; RNF144A; RNF144B; disease

1 Introduction

Ubiquitination, a critical post-translational modification, regulates protein homeostasis through dynamic control of protein stability, subcellular localization, and functional activity ‎‎[1]. Ubiquitination means the binding of ubiquitin molecules to target proteins via a cascade of enzymatic reactions induced by the ubiquitin-proteasome system ‎[2,3]. Ubiquitination enzymes contain ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligase enzymes (E3) ‎[4]. E3 ligases are categorized into four mechanistically distinct classes based on their structural domains: Homologous to E6AP C-Terminus-type (HECT) containing a catalytic HECT domain; RING-type (Really Interesting New Gene) featuring RING finger domains mediating E2 interactions; RING-between-RING-type (RBR) employing a tripartite RING1-IBR-RING2 architecture; PCAF_N-type characterized by N-terminal p300/CBP-associated factor (PCAF) domains ‎[5,6].

The RNF144 family proteins, comprising RNF144A and RNF144B (alternatively designated as PIR2, IBRDC2, and P53RFP), represent a distinct class of RBR E3 ubiquitin ligases. Structural analyses reveal a conserved bipartite architecture: an N-terminal RBR domain (RING1-IBR-RING2) and a C-terminal transmembrane (TM) domain (Figure 1) ‎[7,8,9,10].‎ Mechanistically, the RBR domain facilitates specific E2 ubiquitin-conjugating enzyme recruitment ‎[11], while the TM domain exhibits dual functionality in membrane association and allosteric regulation of ligase activity ‎[7]. Notably, emerging evidence indicates intrinsic functional significance of the TM domain beyond its structural role ‎[12]. Despite growing recognition of RNF144 family involvement in diverse pathological conditions, systematic analyses of their disease-associated mechanisms remain conspicuously absent in current literature. We conducted a literature search in PubMed using the following query terms: “RNF144,” “RNF144A,” “RNF144B,” “PIR2,” “IBRDC2,” and “P53RFP” and ranging from 1982 to 2024. The result of search demonstrates the literatures about RNF144 family proteins were concentrating on recently 10 years. This review comprehensively examines regulatory mechanisms and therapeutic implications of RNF144.

Figure 1 Schematic structure of RNF144A/RNF144B.
Figure 1

Schematic structure of RNF144A/RNF144B.

2 RNF144 family proteins with neurological and psychiatric diseases

The RNF144 protein family demonstrates significant pathophysiological relevance across neurological and psychiatric disorders, including glioma pathogenesis, neural stem cell regulation, schizophrenia susceptibility, and chordoma development (Figure 2).

Figure 2 RNF144A/RNF144B and neurological and psychiatric disorders.
Figure 2

RNF144A/RNF144B and neurological and psychiatric disorders.

2.1 RNF144 family proteins with neurological diseases

The RNF144A expression is lower in glioblastoma than in low-grade gliomas and is negatively correlated with patient survival. The B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), originally characterized as an oncoprotein, executes critical cellular functions through three primary mechanisms: (1) inhibition of premature senescence, (2) maintenance of stem cell self-renewal capacity, and (3) enhancement of cellular stress adaptation ‎[13,14,15]. Within neural systems, BMI1 serves as a key regulator of proliferation in both neural progenitor cells and neural stem cell populations ‎[16]. Notably, RNF144A exhibits a dual regulatory relationship with BMI1, demonstrating negative correlation with BMI1 activation status, and positive association with BMI1 inhibitory signaling pathways ‎[15]. Mechanistic studies employing co-immunoprecipitation assays confirm direct RNF144A-BMI1 physical interaction, through which RNF144A catalyzes BMI1 ubiquitination and subsequent proteasomal degradation ‎[15]. These findings imply RNF144A-mediated ubiquitin-dependent regulation of BMI1 as a potential modulator of neurodevelopmental processes. However, critical molecular details, including precise binding interfaces, ubiquitination acceptor lysine residues, and structural determinants of substrate recognition, remain to be fully elucidated.

The DHHC-family proteins demonstrate significant involvement in glioma pathogenesis ‎[17]. Mechanistic studies reveal that ZDHHC18 and ZDHHC23 competitively link RNF144A to differentially modulate BMI1 polyubiquitination and proteostatic regulation ‎[18]. Experimental manipulation of these DHHC isoforms demonstrates reciprocal functional relationships: ZDHHC18 overexpression attenuates ZDHHC23-RNF144A binding while elevating BMI1 protein levels, and ZDHHC23 overexpression disrupts ZDHHC18-RNF144A interaction while reducing BMI1 abundance ‎[18].

RNF144B can promote chordoma progression ‎[19,20]. Its expression was reported to be up-regulated in chordoma tissues, and knockdown of RNF144B led to inhibition of cell proliferation, migration, and invasion, whose specific mechanisms are to be further explored ‎[20].

2.2 RNF144 family proteins with psychiatric diseases

A genome-wide association study (GWAS) conducted in a cohort of 738 schizophrenia patients receiving standard antipsychotic therapy identified RNF144A as a pharmacogenomic susceptibility locus associated with metabolic adverse effects. Functional annotations demonstrated this gene’s specific involvement in drug-induced triglyceride dysregulation, establishing it as a key mediator of antipsychotic-related metabolic disturbances ‎[21]. Specific mechanisms by which RNF144A regulates schizophrenia are to be further explored.

3 RNF144 family proteins with respiratory diseases

RNF144 demonstrates predominant association with solid tumors of the respiratory system, exhibiting dual roles (Figure 3).

Figure 3 RNF144A/RNF144B and respiratory diseases.
Figure 3

RNF144A/RNF144B and respiratory diseases.

3.1 RNF144 family proteins promote respiratory diseases

A representative case involving a stage IVB lung adenocarcinoma (LUAD) patient harboring the ALK-RNF144A tyrosine kinase fusion demonstrated clinical significance. Following combination therapy with the third-generation ALK inhibitor lorlatinib, paclitaxel, and anlotinib, the patient achieved durable disease stabilization with progression-free survival exceeding 18 months ‎[22]. There is a lack of research on this mechanism of action.

3.2 RNF144 families inhibit respiratory diseases

Integrated multi-omics analysis combining TCGA data mining, Kaplan-Meier survival modeling, and functional enrichment analyses (STRING, GO/KEGG, GSEA) systematically investigated RBR E3 ubiquitin ligases in LUAD pathogenesis ‎[23]. The study identified RNF144B as a clinically relevant biomarker strongly correlated with advanced clinicopathological features and poor prognostic outcomes. Mechanistic multi-omics interrogation revealed RNF144B’s functional engagement in mitochondrial metabolic reprogramming (NADH dehydrogenase complex assembly), ubiquitination machinery (ubiquitin transferase activity), and immune regulation through cytoplasmic nucleic acid sensing (RIG-I-like receptor pathway) and inflammatory signaling (NF-κB pathway) ‎[23]. Complementary functional studies demonstrated that the knockdown of RNF144B in human and murine LUAD models confers proliferative advantage and oncogenic transformation, mediated through cell cycle deregulation, defective DNA damage response, and proteostasis impairment ‎[24]. Importantly, RNF144B deficiency induces chromosomal instability and mitotic catastrophe in LUAD cells, which have been associated with worse prognosis ‎[24]. Unfortunately, none of these studies have elaborated on the pathways and target proteins through which RNF144B regulates LUAD.

4 RNF144 family proteins with digestive system diseases

The RNF144 protein family demonstrates significant pathological associations across digestive system malignancies, including hepatocellular carcinoma (HCC), gastric cancer, and severe acute pancreatitis (SAP) (Figure 4). Functional characterization reveals dual roles of RNF144 family proteins in gastrointestinal oncology.

Figure 4 RNF144A/RNF144B and digestive system diseases.
Figure 4

RNF144A/RNF144B and digestive system diseases.

4.1 RNF144 family proteins promote digestive system diseases

Integrative multi-platform analysis identifies RNF144A as a pathogenic driver in gastric adenocarcinoma, mechanistically linked to its capacity to orchestrate M2 macrophage polarization ‎[25]. Notably, miR-100 overexpression in gastric cancer specimens establishes an oncogenic signaling axis through direct transcriptional activation of RNF144B. This miRNA-mediated regulation triggers ubiquitin-mediated proteasomal degradation of pirh2 (a p53-specific E3 ligase), consequently destabilizing tumor suppressor p53 and driving malignant progression ‎[26].

Comprehensive dataset and bioinformatics analyses identified RNF144A as a dysregulated molecular signature along SAP pathophysiological continuum ‎[27]. The expression of RNF144A was upregulated in SAP, highlighting the potential of using RNF144A as a predictor of SAP prognosis, which is closely associated with a variety of immune cells and may be a feature of regulating immune cell penetration in the microenvironment. This remains to be demonstrated by further in vivo and in vitro experiments. These findings suggest that RNF144A may be a potential target for developing SAP therapies ‎[27].

4.2 RNF144 family proteins inhibit digestive system diseases

Single-cell transcriptomic profiling of CD133+ cancer stem cells identified RNF144A as a somatic mutation hotspot specifically enriched in hepatic metastatic lesions ‎[28]. Mechanistic interrogation revealed a DNA repair regulatory axis involving this E3 ligase: RNF144A mediates ubiquitin-dependent degradation of DNA-PKcs through its canonical catalytic activity, thereby suppressing topoisomerase I (TOP1)-mediated DNA double-strand break repair ‎[29]. This molecular cascade potentiates radiation-induced NK cell activation, ultimately conferring radiosensitization in HCC models ‎[30].

5 RNF144 family proteins with reproductive system diseases

The RNF144 ubiquitin ligase family exhibits broad pathophysiological relevance across reproductive system disorders, spanning gynecological malignancies (epithelioid ovarian carcinoma, hormone receptor-positive breast cancer, endometrial adenocarcinoma) to benign conditions (endometriosis, spermatogonial stem cell dysregulation) (Figure 5). Functional characterization reveals dual roles of RNF144 family proteins in reproductive system diseases.

Figure 5 RNF144A/RNF144B and reproductive system diseases.
Figure 5

RNF144A/RNF144B and reproductive system diseases.

5.1 RNF144 family proteins promote reproductive system diseases

Through multi-dimensional bioinformatics interrogation integrating TCGA-OV, GSE140082, and GSE34526 datasets-encompassing differential transcriptomics, prognostic Cox modeling, pathway topology mapping, PPI network deconvolution, survival meta-analysis, and immunoblot validation, we identified RNF144B as a molecular nexus bridging polycystic ovary syndrome (PCOS) and ovarian carcinogenesis within a shared pathological continuum ‎[31]. RNF144B plays an important role in the oncogenesis and metastatic dissemination of ovarian cancer, and the level of RNF144B is significantly higher in ovarian cancer tissues than in normal ovarian and benign ovarian tumor tissues. RNF144B interacts with p21 and regulates the degradation of the p21/p53 complex. RNF144B overexpression was reported to promote ovarian cancer growth and metastasis by inhibiting the expression of p53/p21/Bax and elevating the expression of Bcl-2 ‎[32].

Integrative analysis of GWAS with cross-platform meta-analyses identified RNF144B as a novel susceptibility locus for endometriosis, though its precise molecular pathophysiology requires functional validation ‎[33]. RNF144B is a potential target biomarker for endometrial cancer. Intriguingly, this E3 ligase exhibits cancer-specific proteomic dysregulation – while maintaining comparable mRNA levels in normal and malignant endometrium, RNF144B protein expression is exclusively detected in endometrial carcinoma specimens ‎[34]. Mechanistically, RNF144B can stabilize the phosphorylation level of GSK3β downstream signaling molecules, and knockdown of the RNF144B gene in endometrial cancer cells inactivated GSK3β, leading to inhibition of cell proliferation ‎[34].

It was shown that RNF144B promotes the proliferation and inhibits the apoptosis of human spermatogonial stem cells through the FCER2/NOTCH1/HES1 pathway. RNF144B interacts with FCER2, which downregulates the expression of the NOTCH2 structural domain N2ICD, while knockdown of human spermatogonial stem cells by RNF144B was revealed to decrease the FCER2, NOTCH2, and HES1 levels ‎[35]. Moreover, RNF144B has been associated with androgen production. In an earlier study, RNA sequencing was used to detect the genes with altered expression in human neural precursor cells induced by dihydroxytestosterone, and it was found that the expression of RNF144B was significantly elevated ‎[36].

5.2 RNF144 family proteins inhibit reproductive system diseases

Immunohistochemistry analyses reveal significant RNF144A downregulation in epithelioid ovarian cancer (EOC) specimens compared to benign controls ‎[37]. Clinically, EOC patients with RNF144A-low tumors exhibit reduced overall survival ‎[35]. The knockdown of RNF144A was reported to significantly enhance sphere formation and upregulate the stem cell markers in EOC cells, whereas RNF144A overexpression had the opposite effects ‎[37]. LIN28B is an RNA-binding protein responsible for the post-transcriptional regulation of the let-7 family of microRNAs in invertebrates and mammals ‎[38] and is highly expressed in progenitor and stem cells ‎[39]. RNF144A was reported to induce the ubiquitinated degradation of LIN28B in EOC cells ‎[37]. It is hypothesized that RNF144A promotes the degradation of LIN28B in EOC, thereby inhibiting the development of EOC, whose authenticity needs to be further investigated.

RNF144A inhibits breast cancer in three ways. Glia maturation factor-γ (GMFG) is a protein that regulates tumor progression, immune response modulation, and the tissue-specific tumor microenvironment ‎[40]. It has been implicated in colorectal cancer, epithelial ovarian cancer, glioblastoma, low-grade glioma, squamous lung cancer, and ocular melanoma ‎[40,41,42]. The transcription of GMFG was regulated by the transcription factor YY1. It was found that RNF144A can interact with YY1 to promote the ubiquitination-dependent degradation of YYI, thus inhibiting the GMFG expression. This mechanism explains how RNF144A inhibits the proliferation, migration, and invasion of breast cancer cells ‎[43].

The RNF144A expression was downregulated in a group of primary breast cancers, and RNF144A overexpression in breast cancer cells inhibited proliferation, colony formation, migration, in vitro invasion, in vivo tumor growth, and metastasis. On the other hand, the knockdown of RNF144A promoted the malignant phenotype of breast cancer cells ‎[44].

It was found that RNF144A interacts with the heat-shock protein family A member 2 (HSPA2), an oncoprotein, and promotes its ubiquitination degradation, thus negatively regulating breast cancer ‎[44]. Methylation of the promoter of RNF144A can silence the RNF144A gene. There is a CpG island in the RNF144A promoter, and knockdown of the endogenous methyl CpG island-binding structural domain 4 (MBD4) of RNF144A in breast cancer upregulated the expression of RNF144A. This suggests that RNF144A is regulated by promoter methylation ‎[45].

6 RNF144 family proteins with hematologic diseases

RNF144 is associated with multiple myeloma, acute myeloid leukemia, and lymphomas (Figure 6). Plasmacytoma variant translocation 1 (PVT1), an interacting partner of tumor suppressor and pro-apoptotic gene silencing in multiple myeloma, was overexpressed in patients with poor prognosis, and inhibition of the PVT1 expression was found to promote the expression of RNF144A, which may be a new research direction in multiple myeloma ‎[46].

Figure 6 RNF144A/RNF144B and hematologic disorders.
Figure 6

RNF144A/RNF144B and hematologic disorders.

RNF144B has been associated with leukemia. Nucleophosmin (NPM) is a multifunctional oligomeric protein involved in liquid-liquid phase separation, ribosome generation, histone chaperones, and transcriptional regulation ‎[47,48]. NPM was downregulated in acute myeloid leukemia myeloid cells ‎[49]. The knockdown of RNF144B significantly lowered the ubiquitination level of NPM and restored the stability of NPM, while RNF144B overexpression promoted the ubiquitination degradation of NPM ‎[49]. In addition, it was found that knockdown of RNF144B, similar to knockdown of p53, accelerated the development of MYC-driven lymphomas, and the mechanism might be associated with cell cycle progression ‎[50].

7 RNF144 family proteins with infectious diseases

RNF144 is associated with antiviral immunity, salmonellosis, lipopolysaccharide (LPS)-induced inflammation, poly(I:C)-induced inflammation, and tuberculosis infection (Figure 7). STING is an interferon-stimulating factor that plays an important role in antiviral immunity. It was found that RNF144A can interact with STING and promote the ubiquitination of its K6 linkage at K236, thereby inducing downstream signaling molecules ‎[51]. RNF144A overexpression was reported to upregulate HSV-1 or cytoplasmic DNA-induced immune responses, while RNF144A knockdown had the opposite effects. RNA144A exhibited a protective effect on the DNA virus-induced viral immunity in mice ‎[51]. By infecting Atlantic salmon with Salmonella, it was found that RNF144A can be strongly induced by Salmonella through the mechanism correlated with the correlation of T cell function as detected by transcriptomics and quantitative PCR ‎[52].

Figure 7 RNF144A/RNF144B and infectious diseases.
Figure 7

RNF144A/RNF144B and infectious diseases.

The expression level of RNF144B was significantly elevated in the peripheral blood mononuclear cells from patients with sepsis, as well as after induction of bone marrow stromal stem cells by LPS. Knockdown of RNF144B in BMDM cells resulted in increased release of inflammatory factors, suggesting that RNF144B can attenuate the inflammatory response caused by sepsis ‎[53]. Mechanistically, RNF144B interacts with TNAK-binding kinase 1 (TBK1), and RNF144B deficiency can lead to impaired TBK1 activation but enhanced NF-κB activation and increased inflammatory factor release ‎[53].

Another study found that RNF144B can inhibit LPS-induced inflammatory response. By interacting with the scaffold/dimerization structural domain of TBK1 through the in-between- ring (IBR) structural domain, RNF144B can inhibit TBK1 phosphorylation and K63-linked ubiquitination, consequently leading to TBK1 inactivation, IRF3 dephosphorylation, and decreased INF-β release. It was reported that the knockdown of RNF144B increased LPS-induced inflammatory responses ‎[54]. However, a study yielded different results: LPS induced the upregulation of RNF144B in human macrophages and human macrophage-like THP-1 cells, the downregulation of RNF144B in HMDM cells, and a decrease in LPS-induced interleukin-1β (IL-1β) release, suggesting that RNF144B facilitates the LPS-induced IL-1β expression ‎[55].

It was found that knockdown of RNF144B resulted in the upregulation of poly(I:C)-induced expression of the transcription factor IRF3 as well as inflammatory factors such as tumor necrosis factor α (TNFα), IL-6, and interferon I (IFN-I). This suggests that RNF144B is a negative regulator of poly(I:C)-induced inflammation ‎[56]. RNF144B has been strongly associated with susceptibility to bovine tuberculosis, and genome-wide association analysis revealed that RNF144B is the gene most associated with single nucleotide polymorphisms on bovine autosomes ‎[57,58].

8 RNF144 family proteins with dermatologic systemic diseases

RNF144B is an important influencer of keratinocyte proliferation and differentiation. RNF144B was found to bind and mediate the proteasomal degradation of ΔNp63α, and knockdown of RNF144B in primary keratinocytes resulted in increased accumulation of p21WAF1/CIP1 and P63 but severely impaired proliferation and differentiation of keratinocytes ‎[59].

Dysregulation of the microRNA-31 (miR-31) expression is associated with the pathogenesis of psoriasis. The microarray determination of miR-31 expression and quantitative detection of the miR-31 target gene expression showed that the expression of RNF144B in the psoriasis group was higher than that of the control group. It was further revealed that RNF144B promotes T-lymphocyte activation by inhibiting the proliferation of dermal mesenchymal stem cells (DMSCs) and thereby participates in the pathogenesis of psoriasis ‎[60].

9 RNF144 family proteins with other diseases

Prognostic indicators of head and neck squamous cell carcinoma (HNSCC) were screened using molecular characterization databases, the TCGA dataset, and the GEO dataset, and the results revealed that RNF144A has significant prognostic value in HNSCC patients and that RNF144A is involved in signaling pathways of protein metabolism and ubiquitination ‎[61]. RNF144A is frequently mutated or epigenetically silenced in cancers, providing a theoretical basis for assessing the loss of function of RNF144A in tumorigenesis ‎[62]. Exposure of mice to oncogenic conditions after the knockdown of RNF144A resulted in an increased incidence of bladder cancer ‎[62]. This is attributed to the fact that RNF144A interacts with PD-L1 in the cytoplasmic membrane and intracellular vesicles and promotes polyubiquitination and degradation of PD-L1, while knockdown of RNF144A can stabilize PD-L1 ‎[62]. Varicella-associated kinase 3 (VRK3) is an ERK negative regulator that inhibits ERK-dependent apoptosis as a means of exerting cytoprotective effects ‎[63,64,65]. It was found that RNF144A can interact with VRK3 to promote the ubiquitination degradation of VRK3, activate ERK, and promote apoptosis, and these effects are intensified under conditions of oxidative stress ‎[63].

When cells were subjected to sustained or severe DNA damage, the expression of RNF144A was elevated in a p53-dependent manner, and RNF144A was found to interact with the catalytic subunits of DNA-dependent protein kinases (DNA-PKcs) in vivo and ex vivo to promote their ubiquitinated degradation ‎[66]. This finding suggests that RNF144A may be involved in the p53-mediated apoptosis by downregulating DNA-PKcs ‎[66]. It was reported that the histone deacetylase inhibitor TMU-35435 induced RNF144A to interact with DNA-PKcs, and RNF144A promoted the ubiquitination of DNA-PKcs as a combined treatment to induce apoptosis and autophagic cell death ‎[67]. Epidermal growth factor receptor (EGFR) belongs to the family of receptor tyrosine kinases (PTKs) ‎[68]. Ligands of EGFR, such as EGF and the transforming growth factor α, can initiate EGFR dimerization, ubiquitination, activation, and endocytosis upon binding to other ligands, and activation of the EGF/EGFR signaling pathway was found to result in cell migration, proliferation, and differentiation ‎[69,70]. RNF144A and EGFR were reported to interact with each other to promote the ubiquitination of EGFR, maintain EGFR protein stabilization, and prolong EGF/EGFR signaling. Knockdown of RNF144A reduced the EGF-dependent cell proliferation ‎[71]. A specific AluYd8 progenitor exists in the intron of the RNF144A gene, and 14 transcribed sequences are initiated in the opposite direction of the RNF144A gene, i.e., antisense transcripts, whose transcriptional activation may interfere with the transcription of the RNF144A gene or block the binding of the transcripts in the promoter ‎[72].

The most common genetic mutation in human cancers is the p53 gene mutation ‎[73]. Isolation and functional analysis of target genes showed that RNF144B is associated with cell cycle control, which is related to the regulation of p21WAF1/CIP1 by RNF144B. As a direct transcription target of p53, the products of p21WAF1 can inhibit cell proliferation by binding directly to the subunits of cell cycle protein-dependent kinase or E2F transcription factors or by inhibiting DNA replication through interaction with the proliferating cell nuclear antigen. RNF144B interacts with and promotes the ubiquitinated degradation of p21WAF1, and HCT116 cells with RNF144B overexpression can lead to decreased p21WAF1 protein expression when exposed to γ-rays. Inhibition of the RNF144B expression by antisense oligonucleotides was reported to lead to accumulation of the p21WAF1 protein ‎[74,75]. It was found that RNF144B induces p53-dependent apoptosis through its C-terminal TCD structural domain, but not through the RING-IBR-RING structural domain, suggesting that this process is not related to the ubiquitination function of RNF144B ‎[10]. In addition, p53-46F, a mutant type of p53, induced higher levels of RNF144B expression than the wild-type p53 ‎[76]. p73 is a p53-related transcription factor belonging to the p53 transcription factor family, and TAp73 and ΔNp73 are two isoforms of p73 (the former pro-apoptotic and the latter inhibiting apoptosis) ‎[77,78,79]. It was reported that TAp73 can induce RNF144B, which then promotes the ubiquitinated degradation of ΔNp73, and this differential regulation maintains the stability of TAp73 and ΔNp73 ‎[80]. This finding provides a therapeutic pathway to enhance the chemosensitivity of tumor cells. Apoptin, which is a protein derived from the chicken anemia virus, can induce cell death in various cancer cells. More specifically, Apoptin induces the expression of TAp73 to result in apoptosis ‎[81]. It was also found that Apoptin induces the expression of RNF144B, leading to degradation of ΔNp73 and activation of the pro-apoptotic target PUMA, which eventually results in cancer cell death ‎[82].

10 Conclusion

RNF144A and RNF144B are “ancient” genes, first reported in 1982 ‎[83], while they are also “time-honored” genes, which are now reported every year ‎[24,‎46]. Their involvement in organ pathologies in almost every system (Table 1) emphasizes their importance in human beings.

Table 1

Role and mechanism of RNF144A/RNF144B in different diseases

Diseases RNF144A/RNF144B Mechanisms Results
Neuropsychiatric system Glioblastoma RNF144A Binds directly to BMI1 and promotes its ubiquitination degradation Negative correlation with patient survival
Gliomas RNF144A ZDHHC18 and ZDHHC23 Competitively interacts with RNF144A to regulate polyubiquitination of BMI1 Negative correlation with patient survival
Schizophrenia RNF144A Influences on antipsychotic drug side effects Triglyceride disorders
Chordoma RNF144B Promotes tumor cell proliferation, colony formation, invasion, migration, epithelial-epithelial mesenchymal transition and glycolysis Promoting the progression of chordoma
Respiratory system LUAD RNF144A Inhibits ALK-RNF144A fusion gene Prolonged patient survival
RNF144B Relates to NADH dehydrogenase complex assembly, ubiquitin protein transferase activity, cytoplasmic DNA sensing pathway, RIG-I like receptor pathway, and NF-κB pathway Significantly associated with clinicopathologic parameters and prognosis in LUAD
RNF144B Mediates cell cycle progression, DNA damage response and protein degradation Suppression of LUAD
Digestive systems HCC RNF144A Promotes ubiquitination of DNA-PKcs, inhibits TOP1, and enhances the radio-anti-HCC effect of NK cell activation Increasing sensitivity of radiation therapy for HCC
SAP RNF144A May modulate the permeability characteristics of immune cells in the microenvironment Predicting the prognosis of SAP
Gastric cancer RNF144A Promotes M2 macrophage migration Oncogenic
RNF144B Mediates ubiquitination degradation of pirh2 and promotes p53 protein degradation Relevant
Reproductive system Epithelioid ovarian carcinoma RNF144A Reduces sphere formation and down-regulation of stem cell markers in EOC cells Relevant
Breast cancers RNF144A Interacts with YY1 and promotes its ubiquitination degradation, thereby inhibiting GMGF expression Inhibition of proliferation, migration and invasion of breast cancer cells
Interacts with HSPA2 and promotes its ubiquitination degradation Suppressing breast cancers
PCOS RNF144B Unknown Relevant
Ovarian cancer RNF144B Interacts with p21 and regulates degradation of the p21/p53 complex to promote Bcl-2 expression Promoting growth and metastasis of ovarian cancer
Endometriosis RNF144B Unknown Relevant
Endometrial cancer RNF144B Stabilizes the phosphorylation level of signaling molecules downstream of GSK3β Promoting cell proliferation
Spermatogonial stem cell proliferation RNF144B Interacts with FCER2 and downregulates the expression of the NOTCH2 structural domain N2ICD Promoting the proliferation of human spermatogonial stem cells
Hematologic system Multiple myeloma RNF144A Possibly relates to PVT1 Relevant
Leukemia RNF144B Promotes ubiquitination degradation of NPMs Relevant
Lymphomas RNF144B Possibly regulates cell cycle progression Relevant
Infectious diseases Antiviral immunity RNF144A Interacts with STING and promotes ubiquitination of its K6 linkage at K236, thereby inducing downstream signaling molecules DNA viruses play a protective role in inducing viral immunity
Atlantic salmon infected with salmonella. RNF144A Strong induction by Salmonella and correlation with T cell function Relevant
Sepsis RNF144B Interacts with TBK1 to inhibit NF-κB activation and reduce inflammatory factor release Reducing the inflammatory response due to sepsis
LPS-induced inflammation RNF144B Interacts with TBK1 and inhibits TBK1 phosphorylation and K63-linked ubiquitination; inactivation of TBK1, dephosphorylation of IRF3, and reduced INF-β release Inhibiting LPS-induced inflammatory response
Unknown Promoting the LPS-induced expression of IL-1β
Poly(I:C)-induced inflammation RNF144B Knockdown of RNF144B leads to upregulation of poly(I:C)-induced expression of the transcription factor IRF3 as well as inflammatory factors such as TNFα, IL-6, and IFN-I Negative regulation of poly(I:C)-induced inflammation
Bovine tuberculosis RNF144B Unknown Relevant
Dermatologic system Keratinogenesis RNF144B Binds and mediates proteasomal degradation of ΔNp63α Stabilizing proliferation and differentiation of keratinocytes
Psoriasis RNF144B Inhibits proliferation of DMSCs to promote T lymphocyte activation Relevant
Head and neck diseases Squamous cell carcinoma RNF144A Participates in signaling pathways involved in protein metabolism and ubiquitination Relevant
Urinary system Bladder cancer RNF144A Interacts with PD-L1 and promotes polyubiquitination and degradation of PD-L1 Suppressing cancer

By collating the literature on RNF144-related literature, we found that it is closely related to tumors. More noteworthy is the bidirectional role of RNF144 in tumors (Table 2, Figure 8). The tumor-promoting conditions and mechanisms are as follows: Formation of the RNF144A-ALK complex leads to RNF144A-promoted LUAD ‎[22]. RNF144A promotes migration of M2 macrophages ‎[25], and RNF144B promotes ubiquitinated degradation of pirh2 ‎[26], which leads to RNF144 promoting gastric cancer. RNF144B promotes p21/p53 degradation in ovarian cancer ‎[32]. RNF144B promotes phosphorylation of GSK3β in endometrial cancer ‎[34]. RNF144B promotes ubiquitination degradation of NPM, which promotes leukemia ‎[49]. RNF144B promotes MYC-driven lymphoma ‎[50]. The tumor suppression and mechanism are as follows: RNF144B promotes the proliferation of tumor cells and also promotes the stabilization of tumor chromosomes, which leads to the suppression of LUAD by RNF144B ‎[24]. RNF144A promotes the ubiquitination of DNA-PKcs and thereby inhibits HCC ‎[29]. RNA144A promotes the degradation of LIN28B and thereby inhibits EOC ‎[37]. RNF144A promotes ubiquitination degradation of YY1 ‎[43], inhibits tumor cell proliferation and migration ‎[44], and promotes ubiquitination degradation of HSPA2 ‎[45], and these mechanisms lead to the inhibition of breast cancer by RNF144A.

Table 2

Dual role of RNF144 in tumors

Promote cancers Inhibit cancers
LUAD: LUAD:
RNF144A-ALK complex formation RNF144B promotes tumor cell proliferation
Gastric cancer: RNF144B promotes tumor chromosome stability
RNF144A promotes M2 macrophage migration HCC:
RNF144B promotes pirh2 ubiquitination degradation RNF144A promotes DNA-PKcs ubiquitination
Ovarian cancer: Ovarian cancer:
RNF144B Promoting p21/p53 degradation RNF144A promotes the degradation of LIN2B
Endometrial cancer: Breast cancer:
RNF144B promotes ubiquitinated degradation of GSK3β RNF144A promotes ubiquitinated degradation of YY1
Leukemia: RNF144A inhibits tumor cell proliferation and migration
RNF144B promotes NPM ubiquitination degradation RNF144A promotes ubiquitination degradation of HSPA2
Lymphomas:
RNF144B promotes the driving role of MYC
Figure 8 The dual roles of RNF144A/RNF144B in tumors.
Figure 8

The dual roles of RNF144A/RNF144B in tumors.

As a result, RNF144 promotes LUAD, gastric cancer, ovarian cancer, endometrial cancer, leukemia, and lymphoma and inhibits LUAD, HCC, ovarian cancer, and breast cancer. In addition, RNF144 is sometimes pro-carcinogenic and sometimes oncogenic in LUAD and ovarian cancer ‎[22,23,24]. The mechanism underlying this phenomenon has been investigated to some extent, including gastric cancer, HCC, breast cancer, and leukemia, which are regulated by RNF144-mediated ubiquitination, and the degradation of p53 and LIN28B in ovarian cancer, which is also supposed to be RNF144-mediated ubiquitination, which needs to be further verified.

In addition to being associated with tumors, RNF144A and RNF144B play important roles in neurological and infectious diseases. Most of the literature demonstrates that RNF144 has an anti-infective effect. When the organism is infected by viral DNA or Salmonella, RNF144 promotes STING activation or modulation of T-cell function and production of interferon, which enhances antiviral immunity ‎[51]. When cells were stimulated by poly(I:C), RNF144 downregulated the release of pro-inflammatory cytokines by an unknown molecular mechanism ‎[56]. Interestingly, RNF144 also had a bidirectional regulatory effect on cells after monocyte-macrophage induction by LPS. Zhang et al. demonstrated that after LPS induction in macrophages, RNF144 promoted ubiquitinated degradation of TBK1, leading to a decrease in interferon release and thus anti-inflammation ‎[54]. Paradoxically, Ariffin et al. found that the release of IL-1β was reduced after LPS-induced RNF144B knockdown macrophages, while it increased after LPS-induced RNF144B overexpressing macrophages and thus pro-inflammatory ‎[55]. This finding has not been verified in great detail, and its mechanism still needs to be further investigated.

In neuropsychiatric disorders, RNF144 has consistent negative effects, promoting tumors, including gliomas and chordomas, or causing side effects from antipsychotics ‎[15‎,18,19,20,21]. Considering the bidirectional regulatory role of RNF144 in other tumors and infectious diseases, it may have a similar role in other neurological disorders, and we can further investigate in this direction.

In addition, we found that RNF144A and RNF144B, although both members of the RNF144 family, do not have identical regulatory roles in relation to disease pathways. In some diseases, they have opposite regulatory roles. For example, in LUAD, RNF144A promotes tumors while RNF144B inhibits them ‎[22,23,24]. In certain diseases, they have coordinated and complementary roles. For example, in gastric cancer, RNF144A and RNF144B jointly promote tumor development by promoting M2 macrophage migration and ubiquitination degradation of pirh2, respectively ‎[25,26]. This should be related to the difference in the number of amino acids or the different TM structural domains at the C-terminus.

Unlike the bidirectional role of RNF144, other RBR E3s usually have a concerted role. For example, parkin, which has been shown to have a promoting effect in tumors such as HCC ‎[84,85], drives apoptosis in HCC cells by inhibiting the NF-κB pathway by promoting the degradation of TRAF2 and TRAF6 ‎[84,86]. HOIP is considered a protective factor for the organism. When HOIP is defective in the organism, it is more likely to acquire immunodeficiency ‎[87]. This is because HOIP increases the ubiquitination of STAT1, which inhibits interferon production ‎[88].

As ubiquitination-associated genes, RNF144A and RNF144B mostly regulate the activity of target proteins and signaling pathways by interacting with these proteins to promote their ubiquitination, mainly by facilitating the assembly of the K6-, K11-, K48-, and K63-linked ubiquitin chains ‎[89]. However, the specific ubiquitination mechanisms of RNF144A and RNF144B in different diseases are currently understudied. There is only one adequate study reporting that RNF144A interacts with STING and promotes the ubiquitination of its K6 linkage at K236, which in turn induces downstream signaling molecules and protects against DNA viruses in inducing viral immunity ‎[51]. Therefore, the mechanism underlying the ubiquitination modification of RNF144A still needs to be further explored, which also provides more research possibilities for developing novel disease-targeted therapies.

Most of the experimental results in the current literature on RNF144 are based on in vitro models, with relatively few in vivo studies, so the conclusions available may be limited. More mice and human specimens will be needed in the future to verify the reliability of these experimental results.

For now, RNF144 is involved in regulatory roles in numerous diseases, and exploring a criterion as a biomarker for diagnosing diseases, especially digestive and reproductive tumors, is worthy of our consideration, and the development of targeted biologics specific for RNF144 is a new direction for targeted therapy. However, as we mentioned earlier, RNF144 has bidirectional roles in tumors and inflammation, which makes it challenging to identify RNF144 as a criterion for disease diagnosis, and there is a long way to go to investigate new drugs targeting RNF144. We need to study the molecular mechanism of RNF144 regulation of diseases more profoundly to provide a reliable theoretical basis for diagnosis and targeted therapy.

# Wang Jiang and Yi Liang contributed equally to this work.

tel: +86-13973166482

Acknowledgments

This work was supported by the Key Laboratory Project of Digestive Diseases in Jiangxi Province (2024SSY06101), and Jiangxi Clinical Research Center for Gastroenterology (20223BCG74011).

  1. Funding information: This work was supported by the Natural Science Foundation of Hunan Province (grant number: 2023JJ30067).

  2. Author contributions: WJ and YS conceived the study. WJ and YL wrote the manuscript. MH, WH, KC, and CD revised the manuscript. YS obtained funding. All authors read and approved the final version of the manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

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Received: 2024-10-23
Revised: 2025-05-07
Accepted: 2025-05-19
Published Online: 2025-08-01

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

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

Articles in the same Issue

  1. Safety assessment and modulation of hepatic CYP3A4 and UGT enzymes by Glycyrrhiza glabra aqueous extract in female Sprague–Dawley rats
  2. Adult-onset Still’s disease with hemophagocytic lymphohistiocytosis and minimal change disease
  3. Role of DZ2002 in reducing corneal graft rejection in rats by influencing Th17 activation via inhibition of the PI3K/AKT pathway and downregulation of TRAF1
  4. Biomedical Sciences
  5. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  6. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  7. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  8. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  9. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  10. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  11. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
  12. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
  13. Battling COVID-19 leveraging nanobiotechnology: Gold and silver nanoparticle–B-escin conjugates as SARS-CoV-2 inhibitors
  14. Neurodegenerative diseases and neuroinflammation-induced apoptosis
  15. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  16. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  17. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  18. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  19. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  20. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  21. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
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  24. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
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  26. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  27. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  28. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
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  30. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  31. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
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  33. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
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https://doi.org/10.1515/biol-2025-1130
Keywords for this article
RNF144; RNF144A; RNF144B; disease
Creative Commons
BY 4.0

Articles in the same Issue

  1. Safety assessment and modulation of hepatic CYP3A4 and UGT enzymes by Glycyrrhiza glabra aqueous extract in female Sprague–Dawley rats
  2. Adult-onset Still’s disease with hemophagocytic lymphohistiocytosis and minimal change disease
  3. Role of DZ2002 in reducing corneal graft rejection in rats by influencing Th17 activation via inhibition of the PI3K/AKT pathway and downregulation of TRAF1
  4. Biomedical Sciences
  5. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  6. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  7. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  8. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  9. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  10. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  11. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
  12. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
  13. Battling COVID-19 leveraging nanobiotechnology: Gold and silver nanoparticle–B-escin conjugates as SARS-CoV-2 inhibitors
  14. Neurodegenerative diseases and neuroinflammation-induced apoptosis
  15. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  16. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  17. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  18. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  19. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  20. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  21. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  22. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  23. Changes in blood glucose and metabolism in hyperuricemia mice
  24. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  25. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  26. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  27. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  28. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  29. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  30. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  31. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  32. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  33. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  34. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  35. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  36. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  37. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  38. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  39. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  40. Low-pressure exposure influences the development of HAPE
  41. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  42. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
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  48. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  49. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  50. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  51. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  52. Sodium butyrate aids brain injury repair in neonatal rats
  53. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  54. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  55. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  56. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  57. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  58. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  59. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  60. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  61. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  62. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  63. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  64. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  65. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  66. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  67. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  68. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  69. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  70. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  71. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  72. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  73. Oncolytic bacteria: A revolutionary approach to cancer therapy
  74. A de novo meningioma with rapid growth: A possible malignancy imposter?
  75. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  76. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  77. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  78. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  79. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  80. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  81. Evaluation and application analysis of animal models of PIPNP based on data mining
  82. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  83. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  84. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  85. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  86. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  87. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  88. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  89. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  90. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  91. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  92. RNF144A and RNF144B: Important molecules for health
  93. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  94. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  95. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  96. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  97. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  98. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  99. Understanding risk factors and prognosis in diabetic foot ulcers
  100. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  101. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  102. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  103. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  104. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  105. Pulmonary cryptococcosis with headache as the first presentation: A case report
  106. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  107. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  108. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  109. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  110. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  111. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  112. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  113. Wound healing and signaling pathways
  114. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  115. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  116. Research progress on the impact of curcumin on immune responses in breast cancer
  117. Biogenic Cu/Ni nanotherapeutics from Descurainia sophia (L.) Webb ex Prantl seeds for the treatment of lung cancer
  118. Dapagliflozin attenuates atrial fibrosis via the HMGB1/RAGE pathway in atrial fibrillation rats
  119. Glycitein alleviates inflammation and apoptosis in keratinocytes via ROS-associated PI3K–Akt signalling pathway
  120. ADH5 inhibits proliferation but promotes EMT in non-small cell lung cancer cell through activating Smad2/Smad3
  121. Apoptotic efficacies of AgNPs formulated by Syzygium aromaticum leaf extract on 32D-FLT3-ITD human leukemia cell line with PI3K/AKT/mTOR signaling pathway
  122. Novel cuproptosis-related genes C1QBP and PFKP identified as prognostic and therapeutic targets in lung adenocarcinoma
  123. Bee venom promotes exosome secretion and alters miRNA cargo in T cells
  124. Treatment of pure red cell aplasia in a chronic kidney disease patient with roxadustat: A case report
  125. Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status
  126. Kynurenine facilitates renal cell carcinoma progression by suppressing M2 macrophage pyroptosis through inhibition of CASP1 cleavage
  127. RFX5 promotes the growth, motility, and inhibits apoptosis of gastric adenocarcinoma cells through the SIRT1/AMPK axis
  128. ALKBH5 exacerbates early cardiac damage after radiotherapy for breast cancer via m6A demethylation of TLR4
  129. Phytochemicals of Roman chamomile: Antioxidant, anti-aging, and whitening activities of distillation residues
  130. Circadian gene Cry1 inhibits the tumorigenicity of hepatocellular carcinoma by the BAX/BCL2-mediated apoptosis pathway
  131. The TNFR-RIPK1/RIPK3 signalling pathway mediates the effect of lanthanum on necroptosis of nerve cells
  132. Longitudinal monitoring of autoantibody dynamics in patients with early-stage non-small-cell lung cancer undergoing surgery
  133. The potential role of rutin, a flavonoid, in the management of cancer through modulation of cell signaling pathways
  134. Construction of pectinase gene engineering microbe and its application in tobacco sheets
  135. Construction of a microbial abundance prognostic scoring model based on intratumoral microbial data for predicting the prognosis of lung squamous cell carcinoma
  136. Sepsis complicated by haemophagocytic lymphohistiocytosis triggered by methicillin-resistant Staphylococcus aureus and human herpesvirus 8 in an immunocompromised elderly patient: A case report
  137. Sarcopenia in liver transplantation: A comprehensive bibliometric study of current research trends and future directions
  138. Advances in cancer immunotherapy and future directions in personalized medicine
  139. Can coronavirus disease 2019 affect male fertility or cause spontaneous abortion? A two-sample Mendelian randomization analysis
  140. Heat stroke associated with novel leukaemia inhibitory factor receptor gene variant in a Chinese infant
  141. PSME2 exacerbates ulcerative colitis by disrupting intestinal barrier function and promoting autophagy-dependent inflammation
  142. Hyperosmolar hyperglycemic state with severe hypernatremia coexisting with central diabetes insipidus: A case report and literature review
  143. Efficacy and mechanism of escin in improving the tissue microenvironment of blood vessel walls via anti-inflammatory and anticoagulant effects: Implications for clinical practice
  144. Merkel cell carcinoma: Clinicopathological analysis of three patients and literature review
  145. Genetic variants in VWF exon 26 and their implications for type 1 Von Willebrand disease in a Saudi Arabian population
  146. Lipoxin A4 improves myocardial ischemia/reperfusion injury through the Notch1-Nrf2 signaling pathway
  147. High levels of EPHB2 expression predict a poor prognosis and promote tumor progression in endometrial cancer
  148. Knockdown of SHP-2 delays renal tubular epithelial cell injury in diabetic nephropathy by inhibiting NLRP3 inflammasome-mediated pyroptosis
  149. Exploring the toxicity mechanisms and detoxification methods of Rhizoma Paridis
  150. Concomitant gastric carcinoma and primary hepatic angiosarcoma in a patient: A case report
  151. YAP1 inhibition protects retinal vascular endothelial cells under high glucose by inhibiting autophagy
  152. Identification of secretory protein related biomarkers for primary biliary cholangitis based on machine learning and experimental validation
  153. Integrated genomic and clinical modeling for prognostic assessment of radiotherapy response in rectal neoplasms
  154. Stem cell-based approaches for glaucoma treatment: a mini review
  155. Bacteriophage titering by optical density means: KOTE assays
  156. Neutrophil-related signature characterizes immune landscape and predicts prognosis of esophageal squamous cell carcinoma
  157. Integrated bioinformatic analysis and machine learning strategies to identify new potential immune biomarkers for Alzheimer’s disease and their targeting prediction with geniposide
  158. TRIM21 accelerates ferroptosis in intervertebral disc degeneration by promoting SLC7A11 ubiquitination and degradation
  159. TRIM21 accelerates ferroptosis in intervertebral disc degeneration by promoting SLC7A11 ubiquitination and degradation
  160. Histone modification and non-coding RNAs in skin aging: emerging therapeutic avenues
  161. A multiplicative behavioral model of DNA replication initiation in cells
  162. Biogenic gold nanoparticles synthesized from Pergularia daemia leaves: a novel approach for nasopharyngeal carcinoma therapy
  163. Creutzfeldt-Jakob disease mimicking Hashimoto’s encephalopathy: steroid response followed by decline
  164. Impact of semaphorin, Sema3F, on the gene transcription and protein expression of CREB and its binding protein CREBBP in primary hippocampal neurons of rats
  165. Iron overloaded M0 macrophages regulate hematopoietic stem cell proliferation and senescence via the Nrf2/Keap1/HO-1 pathway
  166. Revisiting the link between NADPH oxidase p22phox C242T polymorphism and ischemic stroke risk: an updated meta-analysis
  167. Exercise training preferentially modulates α1D-adrenergic receptor expression in peripheral arteries of hypertensive rats
  168. Overexpression of HE4/WFDC2 gene in mice leads to keratitis and corneal opacity
  169. Tumoral calcinosis complicating CKD-MBD in hemodialysis: a case report
  170. Mechanism of KLF4 Inhibition of epithelial-mesenchymal transition in gastric cancer cells
  171. Dissecting the molecular mechanisms of T cell infiltration in psoriatic lesions via cell-cell communication and regulatory network analysis
  172. Circadian rhythm-based prognostic features predict immune infiltration and tumor microenvironment in molecular subtypes of hepatocellular carcinoma
  173. Ecology and Environmental Science
  174. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  175. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  176. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  177. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  178. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  179. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  180. Global assessment of the fate of nitrogen deposition in forest ecosystems: Insights from 15N tracer studies
  181. Fungal and bacterial pathogenic co-infections mainly lead to the assembly of microbial community in tobacco stems
  182. Influencing of coal industry related airborne particulate matter on ocular surface tear film injury and inflammatory factor expression in Sprague-Dawley rats
  183. Temperature-dependent development, predation, and life table of Sphaerophoria macrogaster (Thomson) (Diptera: Syrphidae) feeding on Myzus persicae (Sulzer) (Homoptera: Aphididae)
  184. Eleonora’s falcon trophic interactions with insects within its breeding range: A systematic review
  185. Agriculture
  186. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  187. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  188. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  189. Molecular mechanism of follicular development in laying hens based on the regulation of water metabolism
  190. Molecular identification and control studies on Coridius sp. (Hemiptera: Dinidoridae) in Al-Khamra, south of Jeddah, Saudi Arabia
  191. 10.1515/biol-2025-1218
  192. Animal Science
  193. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  194. Plant Sciences
  195. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  196. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  197. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  198. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  199. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  200. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  201. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  202. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  203. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  204. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  205. Using plant electrical signals of water hyacinth (Eichhornia crassipes) for water pollution monitoring
  206. Response of hybrid grapes (Vitis spp.) to two biotic stress factors and their seedlessness status
  207. Metabolomic profiling reveals systemic metabolic reprogramming in Alternaria alternata under salt stress
  208. Effects of mixed salinity and alkali stress on photosynthetic characteristics and PEPC gene expression of vegetable soybean seedlings
  209. Food Science
  210. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  211. Review on role of honey in disease prevention and treatment through modulation of biological activities
  212. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  213. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  214. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  215. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  216. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  217. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  218. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  219. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  220. The dilemma of food genetics and improvement
  221. Causal effects of trace elements on congenital foot deformities and their subtypes: a Mendelian randomization study with gut microbiota mediation
  222. Honey meets acidity: a novel biopreservative approach against foodborne pathogens
  223. Bioengineering and Biotechnology
  224. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  225. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  226. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  227. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  228. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  229. Fluorescent detection of sialic acid–binding lectins using functionalized quantum dots in ELISA format
  230. Smart tectorigenin-loaded ZnO hydrogel nanocomposites for targeted wound healing: synthesis, characterization, and biological evaluation
  231. Corrigendum
  232. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  233. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
  234. Retraction
  235. Retraction of “Down-regulation of miR-539 indicates poor prognosis in patients with pancreatic cancer”
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