SOX5 promotes cell growth and migration through modulating the DNMT1/p21 pathway in bladder cancer

• Published in: Acta biochimica et biophysica Sinica Vol. 54; no. 7; pp. 987 - 998
• Main Authors: Wu, Longxiang, Yang, Zhongqing, Dai, Guoyu, Fan, Benyi, Yuan, Junbin, Liu, Yalin, Liu, Peihua, Ou, Zhenyu
• Format: Journal Article
• Language: English
• Published: China China Science Publishing & Media Ltd 01.07.2022
• Subjects: bladder cancer; Cell Line, Tumor; Cell Proliferation - genetics; DNA (Cytosine-5-)-Methyltransferase 1 - genetics; DNA (Cytosine-5-)-Methyltransferase 1 - metabolism; DNA methylation; DNMT1; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs - genetics; p21; SOX5; SOXD Transcription Factors - genetics; SOXD Transcription Factors - metabolism; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; DNA methylation; DNMT1; bladder cancer; p21; SOX5
• ISSN: 1672-9145; 1745-7270
• DOI: 10.3724/abbs.2022075

Bladder cancer (BC) is one of the most prevalent and life-threatening cancers among the male population worldwide. Sex determining region Y-box protein 5 (SOX5) plays important roles in a variety of human cancers. However, little research has been conducted on the function and underlying mechanism of SOX5 in BC. In the present study, we first reveal the increased expression of SOX5 in BC tissues and cells lines. Second, we discover that inhibition of SOX5 inhibits cell growth and migration but promotes cell apoptosis. Meanwhile, ectopic SOX5 expression stimulates cell growth and migration in BC cells. Then, we show that suppressing SOX5 inhibits the expression of DNA methyltransferase 1 (DNMT1), and that overexpressing DNMT1 alleviates the cell progress of BC cells inhibited by SOX5. Furthermore, we demonstrate that DNMT1 inhibits p21 expression by affecting DNA methylation of the p21 promoter. Collectively, we demonstrate that SOX5 exerts its functions in BC cells by modulating the SOX5/DNMT1/p21 pathway. Finally, we demonstrate that SOX5 knockdown inhibits xenograft tumor growth . In conclusion, our study elucidates the oncogenic role of SOX5 and its underlying molecular mechanism in BC, and reveals a novel pathway which has the potential to serve as a diagnostic biomarker and therapeutic target for BC.