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image of YBX1 Enhances the Stability of TM4SF1 in an m5C-Dependent Manner to Promote Bladder Cancer Proliferation and Glycolysis

Abstract

Introduction

Y-box binding protein 1 (YBX1), an RNA-binding protein capable of recognizing the 5-methylcytosine (m5C), plays a role in the development and progression of various cancers. In this study, we aim to investigate the functional mechanism of YBX1-mediated m5C modification in Bladder Cancer (BCa).

Methods

The impact of YBX1 on glycolysis and biological functions in BCa cells was evaluated through a set of experiments. The underlying mechanisms involving YBX1, Transmembrane 4 L six family 1 (TM4SF1), and β-catenin/C-myc in BCa and their relationship were investigated using RNA immunoprecipitation (RIP), m5C-RIP, Actinomycin D, and luciferase reporter gene assays.

Results

BCa cells exhibited elevated expression levels of YBX1 compared to human transitional bladder epithelial cells. YBX1 knockdown inhibited BCa cell proliferation, migration, and invasion while also attenuating glycolytic activity, as evidenced by reduced glucose uptake, lactic acid production, and ATP synthesis. Mechanically, we found that YBX1-dependent m5C modification promoted the stability of TM4SF1 mRNA, thereby upregulating TM4SF1 expression and subsequently activating the β-catenin/C-myc signaling. Furthermore, we discovered that overexpression of β-catenin could reverse the inhibitory effects of TM4SF1 silencing on proliferation and glycolysis in BCa cells.

Discussion

This study has refined the mechanism of BCa progression, but the clinical significance and functions of the YBX1/TM4SF1 axis still require further verification.

Conclusion

YBX1 stabilizes TM4SF1 mRNA m5C modification in BCa, activating β-catenin/c-Myc signaling to drive tumor growth and glycolysis. This reveals a novel therapeutic target for BCa.

© 2025 Bentham Science Publishers
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2025-09-26
2025-11-09

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/content/journals/cchts/10.2174/0113862073392269250825105059
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YBX1 Enhances the Stability of TM4SF1 in an m5C-Dependent Manner to Promote Bladder Cancer Proliferation and Glycolysis
Bentham Science Publishers ; https://doi.org/10.2174/0113862073392269250825105059
/content/journals/cchts/10.2174/0113862073392269250825105059
/content/journals/cchts/10.2174/0113862073392269250825105059
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  • Article Type:     Research Article
Keywords: YBX1 ; glycolysis ; Bladder cancer ; TM4SF1 ; proliferation ; m5C

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