4.7 Review

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

Journal

MOLECULAR CANCER
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12943-020-01263-w

Keywords

Cancer; Inhibitors; Anti-cancer therapy; Proliferation; Migration; Epitranscriptome; RNA modifications; N6-methyladenosine; m(6)A; 5-methylcytosine; m(5)C; Pseudouridine; Psi

Funding

  1. Spanish Ministry of Economy and Innovation (MINECO)
  2. Ministry of Science and Innovation
  3. Agencia Estatal de Investigacion (AEI)
  4. European Development Regional Fund (FEDER) [SAF2016-78667-R, PID2019-111692RB-I00]
  5. Scientific Foundation AECC [LABAE19040BLAN]
  6. Junta de Castilla y Leon-Fondo Social Europeo (ESF) predoctoral fellowship
  7. Programa de Apoyo a Planes Estrategicos de Investigacion de Estructuras de Investigacion de Excelencia - Castilla-Leon autonomous government
  8. European Regional Development Fund [CLC-2017-01]

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RNA modifications play a critical role in gene expression regulation, influencing biological processes and disease development, particularly in cancer.
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 N-6-methyladenosine (m(6)A), 5-methylcytosine (m(5)C) and pseudouridine (Psi) 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.

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