Startseite The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
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The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity

  • Zhenshan Ding EMAIL logo , Binbin Jiao , Xuelong Chen , Xing Chen , Yangtian Jiao , Jianfeng Wang und Xiaofeng Zhou EMAIL logo
Veröffentlicht/Copyright: 24. August 2023
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Open Medicine
Aus der Zeitschrift Open Medicine Band 18 Heft 1

Abstract

Bladder cancer is a common malignant tumor. FOXP1 has been found to be abnormally expressed in tumors such as renal cell carcinoma and endometrial cancer. Here, this investigated the biological roles of Foxp1 in the occurrence and development of bladder cancer. Patients with bladder cancer were obtained from China-Japan Friendship Hospital. Bladder cancer cell lines (5637, UMUC3, J82, and T24 cell) were used in this experiment. Foxp1 mRNA and protein expression levels in patients with bladder cancer were increased, compared with paracancerous tissue (normal). OS and DFS of Foxp1 low expression in patients with bladder cancer were higher than those of Foxp1 high expression. Foxp1 promoted bladder cancer cell growth in vitro model. Foxp1 increased the Warburg effect of bladder cancer. Foxp1 suppressed β-adrenoceptor (β-AR) expression in vitro model. ChIP-seq showed that Foxp1 binding site (E1, TTATTTAT) was detected at −2,251 bp upstream of the β-AR promoter. β-AR Reduced the effects of Foxp1 on cell growth in vitro model. β-AR reduced the effects of Foxp1 on the Warburg effect in vitro model by STAT3 activity. Taken together, our findings reveal that Foxp1 promoted the occurrence and development of bladder cancer through the Warburg effect by the activation of STAT3 activity and repressing β-AR transcription, and which might serve as an important clue for its targeting and treatment of bladder cancer.

Keywords: Foxp1; β-AR; STAT3; bladder cancer; Warburg effect

1 Introduction

Bladder cancer is one of the most common malignant tumors in the urogenital system, which ranks ninth among the most common malignant tumors in Europe and the United States [1]. In recent years, the incidence and mortality of bladder cancer in China are on the rise in China [2]. Bladder cancer can occur at any age, with a high incidence in men over 65 years of age [3]. In addition, the incidence ratio of males to females is 3:1–4:1 [4]. Clinically, about 70% of bladder cancers are non-invasive and 30% are invasive [5,6]. Among them, non-muscular invasive bladder cancer is characterized by a high recurrence rate and low mortality, whereas approximately 50% of invasive bladder cancer is potentially fatal [5].

Because of the uncertainty of the immune system in regulating the growth of solid tumors, whether the stress hormones released by the sympathetic nervous system can directly affect the proliferation and metastasis potential of tumor cells has become a research hotspot in recent years. A large number of studies have found that the increased neuropeptides and neurotransmitters produced by the body under stress can change the biological behavior of tumor cells in various stages of tumor progression and metastasis. The neurotransmitter released by the sympathetic postganglionic fibers of the human body is mainly norepinephrine, which acts on β-adrenoceptor (β-AR) and plays a regulatory role. Research shows that the β-AR signal pathway is closely related to the occurrence and development of tumors.

β-AR is a class of intracellular proteins that plays a role in the invasion and metastasis of tumor cells by mediating the desensitization of seven transmembrane-coupled receptors [7]. It can also regulate the corresponding signal pathways through the phosphorylation, ubiquitination, or intracellular localization of other signal molecules [8]. Moreover, β-AR regulates the life course of tumor cells by playing different roles in the corresponding signal pathways [9].

FOXP1, a member of the FOX family, is involved in cardiomyocyte development, immune B cell differentiation, and motor neuron diversity [10]. It is found that FOXP1 is abnormally expressed in various tumors such as breast cancer, lung cancer, bladder cancer, and lymphoma, which may become a tumor marker for clinical practice [11,12]. PBRM1 is a chromatin complex protein that is abnormally expressed in tumors such as renal cell carcinoma and endometrial cancer, which is associated with the occurrence and development of tumors [13,14]. Here, we investigate the biological roles of Foxp1 in the occurrence and development of bladder cancer.

2 Materials and methods

2.1 Experimental clinical medicine

Patients with bladder cancer (n = 41) and paracancerous tissue (n = 41) were obtained from the China-Japan Friendship Hospital from May 2017 to Mar 2018. Tissue samples were collected and saved at −80°C. Overall survival and disease-free survival were executed and followed for 3 years.

  1. Ethics approval and consent to participate: All patients were informed and signed informed consent voluntarily. This study was approved by the ethics committee of the China-Japan Friendship hospitals and complied with the guidelines outlined in the Declaration of Helsinki were followed. The written consent was received from all participants.

2.2 Cell culture and transfection

Normal bladder epithelial cells (GES-1 cell), and bladder cancer cell lines (5637, UMUC3, J82, and T24 cell) were cultured in RPMI 1640 medium (Gibco, Carlsbad, CA, USA) supplemented with 10% fetal calf serum (FCS, Gibco, Carlsbad, CA, USA) in a humidified atmosphere of 5% CO2 at 37°C. Plasmids were transfected into cell using Lipofectamine 2000 as literature [15].

2.3 Microarray analysis

Total RNA was extracted from serum samples, and the amount of RNA was quantified by use of NanoDrop 1000. The total RNA of each sample was used for reverse transcription using an Invitrogen SuperScript double-stranded cDNA synthesis kit. Double-stranded cDNA was executed with a NimbleGen one-color DNA labeling kit and then executed for array hybridization using the NimbleGen hybridization system and washing with the NimbleGen wash buffer kit. Axon GenePix 4000B microarray scanner (Molecular Devices) was used for scanning as literature [16].

2.4 Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR)

Total cellular RNA was extracted using Trizol (Thermo Fisher Scientific) from serum, lung tissue, or cells. RNA was then reverse transcribed into cDNA using Moloney murine leukemia virus reverse transcriptase. The mRNA expression was quantified using 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, CA) and SYBR® Premix Ex TaqTM II (Takara, Japan). Relative gene expression was normalized to GAPDH.

2.5 Cell viability assay

After 48 h of transfection, 1 × 103 cells/well were seeded in a 96-well plate. After culturing at the indicated time (0, 6, 12, 24, and 48 h), the cellular proliferation was detected using Cell Counting Kit-8 (CCK-8, Beyotime, Beijing, China) by CellTiter-GloR Luminescent Cell Viability Assay according to manufacturer’s

2.6 EdU assay

About 50 μM of EdU was used to incubate at 37°C for 1 h, fixed with 4% paraformaldehyde for 15 min, and then stained with DAPI for 15 min. The images were captured under fluorescence microscopy (Nikon, Melville, NY, US).

2.7 Western blot analysis

Total protein lysates from cell samples were solubilized in SDS-PAGE sample buffer using Radio‐Immunoprecipitation Assay and PMSF reagent, separated on a 10% SDS-polyacrylamide gel, and transferred electrophoretically onto polyvinylidenedifluoride (PVDF) membranes. The membranes were blocked with non-fat-milk (5%) for 2 h at room temperature and incubated with anti-Foxp1, anti-β-AR, anti-STAT3, anti-p-STAT3, and anti-β-actin antibodies at 4°C. The membranes were incubated with horseradish peroxide-coupled sheep anti-mouse secondary antibody at room temperature for 2 h. The bound antibodies were detected using enhanced chemiluminescence (ECL) with β-actin used as a control. Band intensities were quantified using Image J software.

2.8 ChIP-seq analysis assay

Cells (1 × 104) were cross-linked with 1% formaldehyde at room temperature for 10 min and incubated with 125 mM glycine for 5 min. Cells were sonicated on ice to generate DNA fragments. The fragmented chromatin fragments were immunoprecipitated with protein A/G magnetic beads (Millipore) coupled with anti-Foxp1 antibody at 4°C overnight with rotation. Input DNA libraries were generated using the NEBNext Ultra II DNA Library Prep Kit for Illumina (E7645, NEB). DNA libraries were used for DNA libraries.

2.9 Statistical analysis

All data are presented as mean ± SEM. Statistics was analyzed by using SPSS 22.0 software (SPSS, Chicago, IL, USA). The unpaired t-test was used for comparisons between two groups, and ANOVA followed by Tukey’s post hoc analysis was used for comparisons between multiple groups or Student’s t test (two groups). A probability value p < 0.05 was considered to be statistically significant.

3 Results

3.1 Foxp1 expression levels in patients with bladder cancer

This work first examines the Foxp1 expression levels in patients with bladder cancer. Foxp1 mRNA and protein expression levels in patients with bladder cancer were increasing, compared with paracancerous tissue (normal) (Figure 1a and b). According to our results, Foxp1 mRNA expression level in paracancerous tissue was lower than that of I–II patients with bladder cancer, and Foxp1 mRNA expression of I–II patients with bladder cancer was lower than that of III–IV patients with bladder cancer (Figure 1c). Foxp1 mRNA expression level in GES-1 cells was lower than those of bladder cancer cell lines (Figure 1d). As a result, OS and DFS of Foxp1 low expression in patients with bladder cancer were higher than those of Foxp1 high expression (Figure 1e and f). Taken together, our data suggest that Foxp1 played a repair factor in bladder cancer.

Figure 1 Foxp1 expression levels in patients with bladder cancer. (a–c) Foxp1 mRNA and protein expression in patients with bladder cancer; (d) Foxp1 mRNA in bladder cancer lines; (e and f) overall survival and disease-free survival in patients with bladder cancer. Normal, normal group; bladder cancer, patients with bladder cancer; **p < 0.01 compared with normal group or GES-1.
Figure 1

Foxp1 expression levels in patients with bladder cancer. (a–c) Foxp1 mRNA and protein expression in patients with bladder cancer; (d) Foxp1 mRNA in bladder cancer lines; (e and f) overall survival and disease-free survival in patients with bladder cancer. Normal, normal group; bladder cancer, patients with bladder cancer; **p < 0.01 compared with normal group or GES-1.

3.2 Foxp1 promoted bladder cancer cell growth in vitro model

Thereafter, we examined the function of Foxp1 on cell growth of bladder cancer cell lines. It was found that Foxp1 plasmid increased the expression of Foxp1 mRNA level in bladder cancer cell (Figure 2a). Si-Foxp1 reduced Foxp1 mRNA level in bladder cancer cells (Figure 2b). Over-expression of Foxp1 promoted cell growth of bladder cancer cells, and down-regulation of Foxp1 reduced cell growth of bladder cancer cell (Figure 2c and d). Over-expression of Foxp1 promoted the migration rate and number of EDU cells in bladder cancer cells (Figure 2e and f). Down-regulation of Foxp1 reduced the migration rate and number of EDU cells in bladder cancer cells (Figure 2g and h). Therefore, we focused Foxp1-promoted cell growth and migration rate of bladder cancer.

Figure 2 Foxp1 promoted bladder cancer cell growth in vitro model. (a and b) Foxp1 mRNA expression, (c and d) cell growth (CCK-8), (e and f) migration rate and EDU assay (d) in vitro model of over-expression of Foxp1, (g and h) migration rate and EDU assay (d) in vitro model of down-regulation of Foxp1. Vector, negative control group; Foxp1, over-expression of Foxp1 group; Si-nc, si-negative control group; Si-Foxp1, downregulation of Foxp1 group; **p < 0.01 compared with negative control group or si-negative control group.
Figure 2

Foxp1 promoted bladder cancer cell growth in vitro model. (a and b) Foxp1 mRNA expression, (c and d) cell growth (CCK-8), (e and f) migration rate and EDU assay (d) in vitro model of over-expression of Foxp1, (g and h) migration rate and EDU assay (d) in vitro model of down-regulation of Foxp1. Vector, negative control group; Foxp1, over-expression of Foxp1 group; Si-nc, si-negative control group; Si-Foxp1, downregulation of Foxp1 group; **p < 0.01 compared with negative control group or si-negative control group.

3.3 Foxp1 increased Warburg effect of bladder cancer

As a next step in investigating the function of Foxp1 on the Warburg effect of bladder cancer. Over-expression of Foxp1 promoted glucose consumption, lactate production, and ATP quantity in bladder cancer cells (Figure 3a–c). Downregulation of Foxp1 reduced glucose consumption, lactate production, and ATP quantity of bladder cancer cells (Figure 3a–c). Furthermore, over-expression of Foxp1 promoted extracellular acidification rate (ECAR) and OCR relative level of bladder cancer cells (Figure 3d and f). Down-regulation of Foxp1 reduced ECAR and OCR-relative levels of bladder cancer cells (Figure 3e and g). These results suggest that Foxp1 could increase the Warburg effect to promote cell growth and migration rate of bladder cancer.

Figure 3 Foxp1 increased the Warburg effect of bladder cancer. Glucose consumption analysis revealed (a) glucose consumption, (b) lactate production analysis revealed lactate production, (c) ATP quantity analysis revealed the ATP quantity, (d and e) ECAR analysis for lactate-induced acidification of the medium surrounding cells, and (f and g) OCR analysis for mitochondrial respiratory capacity was conducted using Seahorse XFp assay. Vector, negative control group; Foxp1, over-expression of Foxp1 group; Si-nc, si-negative control group; Si-Foxp1, downregulation of Foxp1 group; **p < 0.01 compared with negative control group or si-negative control group.
Figure 3

Foxp1 increased the Warburg effect of bladder cancer. Glucose consumption analysis revealed (a) glucose consumption, (b) lactate production analysis revealed lactate production, (c) ATP quantity analysis revealed the ATP quantity, (d and e) ECAR analysis for lactate-induced acidification of the medium surrounding cells, and (f and g) OCR analysis for mitochondrial respiratory capacity was conducted using Seahorse XFp assay. Vector, negative control group; Foxp1, over-expression of Foxp1 group; Si-nc, si-negative control group; Si-Foxp1, downregulation of Foxp1 group; **p < 0.01 compared with negative control group or si-negative control group.

3.4 Foxp1 suppressed β-AR expression in vitro model

Subsequently, to observe any potential mechanism of Foxp1 in bladder cancer, we examined gene expression levels by Foxp1 using microarray analysis and β-AR expression may be one important target for Foxp1 on cell growth of bladder cancer (Figure 4a and b). β-AR mRNA and protein expression were reduced in patients with bladder cancer (Figure 4c and d). β-AR mRNA expression level in paracancerous tissue was higher than that of I–II patients with bladder cancer, and β-AR mRNA expression of I–II patients with bladder cancer was higher than that of III-IV patients with bladder cancer (Figure 4e). The mRNA of β-AR was a negative correlation with serum Foxp1 levels in patients with bladder cancer (Figure 4f). β-AR mRNA expression level in GES-1 cells was higher than those of bladder cancer cell lines (Figure 4g).

Figure 4 Foxp1 suppressed β-AR expression in vivo. Microarray analysis, result diagram, and KEGG terms (a and b), (c–e) β-AR mRNA and protein expression in patients with bladder cancer; (f) correlation between Foxp1 and β-AR in patients with bladder cancer; (g) β-AR mRNA expression in bladder cancer cell lines. Normal, normal group; Bladder cancer, patients with bladder cancer; **p < 0.01 compared with normal group or GES-1.
Figure 4

Foxp1 suppressed β-AR expression in vivo. Microarray analysis, result diagram, and KEGG terms (a and b), (c–e) β-AR mRNA and protein expression in patients with bladder cancer; (f) correlation between Foxp1 and β-AR in patients with bladder cancer; (g) β-AR mRNA expression in bladder cancer cell lines. Normal, normal group; Bladder cancer, patients with bladder cancer; **p < 0.01 compared with normal group or GES-1.

Next, over-expression of Foxp1 reduced β-AR mRNA expression in vitro model (Figure 5a). Down-regulation of Foxp1 induced β-AR mRNA expression in vitro model (Figure 5b). Over-expression of Foxp1 induced Foxp1 protein expression and suppressed β-AR protein expression in vitro model (Figure 5c–e). Down-regulation of Foxp1 suppressed Foxp1 protein expression and induced β-AR protein expression in vitro model (Figure 5f–h). ChIP-seq showed that Foxp1 binding site (E1 and TTATTTAT) was detected at −2,251 bp upstream of the β-AR promoter (Figure 5i and j). In general, data suggest that β-AR is one important targets of Foxp1 in bladder cancer.

Figure 5 (a and b) Foxp1 suppressed β-AR expression in vitro model. β-AR mRNA expression, (c–e) Foxp1 and β-AR protein expression in vitro model of over-expression of Foxp1, (f–h) Foxp1 and β-AR protein expression in vitro model of down-regulation of Foxp1. Foxp1 binding site at −2,251 bp upstream of β3-AR gene promoter with a schematic drawing (i and j). Vector, negative control group; Foxp1, over-expression of Foxp1 group; Si-nc, si-negative control group; Si-Foxp1, downregulation of Foxp1 group; **p < 0.01 compared with negative control group or si-negative control group.
Figure 5

(a and b) Foxp1 suppressed β-AR expression in vitro model. β-AR mRNA expression, (c–e) Foxp1 and β-AR protein expression in vitro model of over-expression of Foxp1, (f–h) Foxp1 and β-AR protein expression in vitro model of down-regulation of Foxp1. Foxp1 binding site at −2,251 bp upstream of β3-AR gene promoter with a schematic drawing (i and j). Vector, negative control group; Foxp1, over-expression of Foxp1 group; Si-nc, si-negative control group; Si-Foxp1, downregulation of Foxp1 group; **p < 0.01 compared with negative control group or si-negative control group.

3.5 β-AR reduced the effects of Foxp1 on cell growth in vitro model

The study determined the role of β-AR controlling the effects of Foxp1 on cell growth and the Warburg effect of bladder cancer. β-AR plasmid increased β-AR protein expression, and reduced cell growth, migration rate and number of EDU cells of bladder cancer cells (Figure 6a–e). β-AR inhibitor Oxprenolol hydrochloride (10 nM) suppressed β-AR protein expression and promoted cell growth, migration rate, and number of EDU cells of bladder cancer cells (Figure 6f–j).

Figure 6 β-AR reduced the effects of Foxp1 on cell growth in vivo or vitro model by STAT3 activity. (a and b) β-AR protein expression, (c) cell growth (CCK-8), (d) migration rate, (e) EDU assay in vitro model of over-expression of Foxp1 and β-AR; (f and g) β-AR protein expression, (h) cell growth (CCK-8), (i) migration rate, (j) EDU assay in vitro model of down-regulation of Foxp1 and β-AR. Vector, negative control group; Foxp1, over-expression of Foxp1 group; β-AR, over-expression of β-AR group; Si-nc, si-negative control group; Si- Foxp1, down-regulation of Foxp1 group; β-AR i, β-AR inhibitor group. **p < 0.01 compared with negative control group or si-negative control group; ## p < 0.01 compared with Foxp1 or si-Foxp1 group.
Figure 6

β-AR reduced the effects of Foxp1 on cell growth in vivo or vitro model by STAT3 activity. (a and b) β-AR protein expression, (c) cell growth (CCK-8), (d) migration rate, (e) EDU assay in vitro model of over-expression of Foxp1 and β-AR; (f and g) β-AR protein expression, (h) cell growth (CCK-8), (i) migration rate, (j) EDU assay in vitro model of down-regulation of Foxp1 and β-AR. Vector, negative control group; Foxp1, over-expression of Foxp1 group; β-AR, over-expression of β-AR group; Si-nc, si-negative control group; Si- Foxp1, down-regulation of Foxp1 group; β-AR i, β-AR inhibitor group. **p < 0.01 compared with negative control group or si-negative control group; ## p < 0.01 compared with Foxp1 or si-Foxp1 group.

3.6 β-AR reduced the effects of Foxp1 on the Warburg effect in vitro model by STAT3 activity

Next, this work investigated the mechanism of Foxp1/β-AR on the Warburg effect of bladder cancer. β-AR plasmid suppressed p-STAT3 protein expression in bladder cancer cell (Figure 7a). β-AR inhibitor Oxprenolol hydrochloride (10 nM) induced p-STAT3 protein expression in bladder cancer cells (Figure 7b). β-AR plasmid reversed the effects of Foxp1 on glucose consumption, lactate production, ATP quantity, ECAR, and OCR relative levels in bladder cancer cells (Figure 7c–g). β-AR inhibitor also reversed the effects of si-Foxp1 on glucose consumption, lactate production, ATP quantity, ECAR, and OCR relative levels in bladder cancer cells (Figure 7h–l).

Figure 7 β-AR reduced the effects of Foxp1 on the Warburg effect in vivo or vitro model by STAT3 activity. p-STAT3 protein expression (a and b); glucose consumption, lactate production, ATP quantity, ECAR, and OCR relative levels in a bladder cancer cell by over-expression of Foxp1 and β-AR (c–g); glucose consumption, lactate production, ATP quantity, ECAR, and OCR relative levels in a bladder cancer cell by downregulation of Foxp1 and β-AR (h–l). Vector, negative control group; Foxp1, over-expression of Foxp1 group; β-AR, over-expression of β-AR group; Si-nc, si-negative control group; Si- Foxp1, downregulation of Foxp1 group; β-AR i, β-AR inhibitor group. **p < 0.01 compared with a negative control group or si-negative control group, ## p < 0.01 compared with Foxp1 or si-Foxp1 group.
Figure 7

β-AR reduced the effects of Foxp1 on the Warburg effect in vivo or vitro model by STAT3 activity. p-STAT3 protein expression (a and b); glucose consumption, lactate production, ATP quantity, ECAR, and OCR relative levels in a bladder cancer cell by over-expression of Foxp1 and β-AR (c–g); glucose consumption, lactate production, ATP quantity, ECAR, and OCR relative levels in a bladder cancer cell by downregulation of Foxp1 and β-AR (h–l). Vector, negative control group; Foxp1, over-expression of Foxp1 group; β-AR, over-expression of β-AR group; Si-nc, si-negative control group; Si- Foxp1, downregulation of Foxp1 group; β-AR i, β-AR inhibitor group. **p < 0.01 compared with a negative control group or si-negative control group, ## p < 0.01 compared with Foxp1 or si-Foxp1 group.

4 Discussion

Bladder cancer is one of the common malignant tumors in the urinary system [17]. Non-muscle invasive bladder cancer refers to the bladder tumor confined to the subepithelial connective tissue without muscular invasion [18]. Early diagnosis is currently emphasized internationally [19]. Transurethral bladder tumor resection combined with bladder perfusion therapy in the early stage can prevent the progression and recurrence of non-invasive bladder cancer [19]. In this study, we examined Foxp1 mRNA and protein expression levels in patients with bladder cancer were increased, compared with paracancerous tissue. Wang et al. demonstrated that FOXP1 serves as a prognostic biomarker for gallbladder cancer progression [20]. We suggest that Foxp1 played a repair factor in bladder cancer cell growth.

Warburg effect is known as the anaerobic glycolysis of tumor cells regardless of whether the environment is oxygen-reorganized or not [21]. Warburg effect enables the tumor cells to obtain more glucose and produce energy, thereby promoting metastasis and invasion [22]. In addition, it can lead to an increase of apoptotic resistance of tumor cells [23]. In the glycolysis reaction, the high expression of enzymes such as PDKs and LDH can provide resistance to tumor apoptosis, which can promote the apoptosis of tumor cells separated from the cellular mechanism and prolong the survival period [24]. Surprisingly, we also observed Foxp1 promoted cell growth and increased Warburg effect in vitro model of bladder cancer. Fang et al. demonstrated that the novel FOXP1 has a role in renal cell carcinoma progression by the Warburg effect [10]. These results suggest that Foxp1 promoted the Warburg effect of bladder cancer.

β-AR is a multifunctional protein that not only participates in the transduction regulation of the GPCR signaling pathway but also plays the role of signal transduction, scaffold protein, or reactive molecule in other pathways [25]. Because of its important intermediate role in the occurrence, proliferation, and metastasis of tumor cells, it has gradually received attention in the medical field [26]. Our study showed that Foxp1 suppressed β-AR expression in vitro model. Foxp1 binding site was detected at −2,251 bp upstream of the β-AR promoter. Liu et al. reveal Foxp1 represses β3-AR transcription [25]. Of note, β-AR it is possible that the effects of Foxp1 may be the promoter factor for bladder cancer progress.

Recent studies have found that STAT3 may promote the Warburg effect in breast cancer and other tumor cells by regulating the expression of glucose transporter 1, pyruvate dehydrogenase, and hexokinase 2 [27,28]. These results of this study suggest that β-AR reduced the effects of Foxp1 on the Warburg effect in vitro model by STAT3 activity. Stapel et al. showed that STAT3 expression sensitizes to the toxic effects of β-AR stimulation in peripartum cardiomyopathy [29]. Sun et al. reported that the STAT3 gene was a transcriptional regulator of FOXP1 [30]. Expectedly, Foxp1 promoted STAT3 activity to heighten the Warburg effect by β-AR in a model of bladder cancer.

In conclusion, Foxp1 promoted occurrence and development of bladder cancer through the Warburg effect by the activation of STAT3 activity and repressing β-AR transcription. This experiment submits that further investigation into mechanisms underlying β-AR-mediated STAT3 regulation by Foxp1 will cast new light upon the Warburg effect of therapeutic strategies for bladder cancer. This study provided a new mechanism for understanding the Foxp1-indicated novel target for bladder cancer treatment. Foxp1 is potential target to be used in the treatment of bladder cancer.

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Acknowledgements

Not applicable.

  1. Funding information: Not applicable.

  2. Author contributions: ZSD designed the experiments. BBJ, XLC, and XC performed the experiments. YTJ, JFW, and XFZ collected and analyzed the data. ZSD and XFZ drafted the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: Not applicable.

  4. Data availability statement: The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-10-14
Revised: 2022-12-25
Accepted: 2023-01-03
Published Online: 2023-08-24

© 2023 the author(s), published by De Gruyter

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

Artikel in diesem Heft

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  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
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  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
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  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
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  233. Case Reports
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  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0647
Schlagwörter für diesen Artikel
Foxp1; β-AR; STAT3; bladder cancer; Warburg effect
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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