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. 2021 May;124(10):1621-1622.
doi: 10.1038/s41416-021-01314-z. Epub 2021 Mar 15.

RNA N6-methyladenosine: a new player in autophagy-mediated anti-cancer drug resistance

Arumugam Paramasivam  1 , Jayaseelan Vijayashree Priyadharsini  2
Affiliations

RNA N6-methyladenosine: a new player in autophagy-mediated anti-cancer drug resistance

Arumugam Paramasivam et al. Br J Cancer. 2021 May.

Abstract

Dysregulation of N6-methyladenosine (m6A) modification is associated with cancer development and progression. The m6A modification plays a crucial role in autophagy regulation precipitating anti-cancer drug resistance. In line with this fact, this commentary discusses m6A modification interfering with autophagy machinery as a major contributing factor for drug resistance in cancer.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Role of m6A modification in sorafenib resistance by modulating autophagy in hepatocellular carcinoma (HCC).
a The m6A “writer” METTL3 sensitises HCC cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner. m6A is deposited on FOXO3 mRNA by METTL3 and translated by YTHDF1, further increased FOXO3 downregulates the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and ATG16L1, thereby, inhibition of autophagy promotes the death of HCC cells. b Depletion of METTL3 and FOXO3 promote autophagy associated sorafenib resistance in HCC.
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