m6A-mediated upregulation of lncRNA RMRP boosts the progression of bladder cancer via epigenetically suppressing SCARA5

Epigenomics. 2023 Apr;15(7):401-415. doi: 10.2217/epi-2023-0062. Epub 2023 Jun 20.

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: DNMTs; RMRP; SCARA5; bladder cancer; hypermethylation; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mice
  • Mice, Nude
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism
  • Transcriptional Activation
  • Up-Regulation
  • Urinary Bladder Neoplasms* / genetics

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • METTL3 protein, human
  • Methyltransferases
  • SCARA5 protein, human
  • Scavenger Receptors, Class A
  • SCARA5 protein, mouse