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

Longxiang Wu; Zhongqing Yang; Guoyu Dai; Benyi Fan; Junbin Yuan; Yalin Liu; Peihua Liu; Zhenyu Ou

doi:10.3724/abbs.2022075

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

Acta Biochim Biophys Sin (Shanghai). 2022 Jun 25;54(7):987-998. doi: 10.3724/abbs.2022075.

Authors

Longxiang Wu^{1

2}, Zhongqing Yang^{1

2}, Guoyu Dai^{1

2}, Benyi Fan^{1

2}, Junbin Yuan^{1

2}, Yalin Liu^{2

3}, Peihua Liu^{1

2}, Zhenyu Ou^{1

2}

Affiliations

¹ Department of Urology, Xiangya Hospital, Central South University, Changsha 410008, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
³ Xiangya School of Medicine, Central South University, Changsha 410008, China.

Abstract

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 in vitro 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 vivo. 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.

Keywords: DNA methylation; DNMT1; SOX5; bladder cancer; p21..

MeSH terms

Cell Line, Tumor
Cell Proliferation / genetics
DNA (Cytosine-5-)-Methyltransferase 1 / genetics
DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
Gene Expression Regulation, Neoplastic
Humans
Male
MicroRNAs* / genetics
SOXD Transcription Factors / genetics
SOXD Transcription Factors / metabolism
Urinary Bladder Neoplasms* / genetics
Urinary Bladder Neoplasms* / pathology

Substances

MicroRNAs
SOX5 protein, human
SOXD Transcription Factors
DNA (Cytosine-5-)-Methyltransferase 1
DNMT1 protein, human

Grants and funding

This work was supported by the grants from the Youth Science Foundation of Xiangya Hospital, Central South University (No. 2019Q09), the Natural Science Foundation of Changsha (No. kq2014274), the Natural Science Foundation of Hunan Province (Nos. 2020JJ5916, 2022JJ40826, and 2021JJ31082) and the National Natural Science Foundation of China (No. 82103298).