The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

Mol Cancer. 2021 Jan 18;20(1):18. doi: 10.1186/s12943-020-01263-w.

Abstract

RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

Keywords: 5-methylcytosine; Anti-cancer therapy; Cancer; Epitranscriptome; Inhibitors; Migration; N6-methyladenosine; Proliferation; Pseudouridine; RNA modifications; m5C; m6A; Ψ.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 5-Methylcytosine / metabolism*
  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / therapy*
  • Pseudouridine / metabolism*
  • RNA / metabolism*
  • RNA Processing, Post-Transcriptional / genetics*

Substances

  • Pseudouridine
  • RNA
  • 5-Methylcytosine
  • N-methyladenosine
  • Adenosine