m⁶A-Mediated Upregulation of lncRNA RMRP Boosts the Progression of Bladder Cancer Via Epigenetically Suppressing SCARA5

Abstract

Aim: This study aimed to elucidate the relationship between SCARA5 and RMRP in bladder cancer and their underlying mechanism. Methods: Biological functions were evaluated using cell-counting kit 8 assay, 5-ethynyl-2’-deoxyuridine incorporation, wound healing and Transwell assays. RNA immunoprecipitation, RNA pull-down and chromatin immunoprecipitation were employed. A xenograft tumor model in nude mice was also conducted. Results & conclusion:RMRP and SCARA5 exhibited an inverse correlation. Downregulation of RMRP significantly suppressed bladder cancer cell proliferation, migration and invasion, which was reversed by SCARA5 overexpression. RMRP recruited DNA methyltransferases to the promoter region of SCARA5, thereby triggering the methylation of the SCARA5 promoter to epigenetically suppress its expression. Our findings elucidate the machinery by which RMRP, stabilized by METTL3, exerts a promoter role in bladder cancer tumorigenesis by triggering SCARA5 methylation.

Keywords::

• bladder cancer
• DNMTs
• hypermethylation
• RMRP
• SCARA5
• tumorigenesis

Financial & competing interests disclosure

This study was supported by Natural Science Foundation of Hunan Province (No.2023JJ30545). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal experiments were approved by the Ethics Committee of The First Affiliated Hospital of the University of South China.

Additional information

Funding

This study was supported by Natural Science Foundation of Hunan Province (No.2023JJ30545). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.