Novel insights into the interplay between m6A modification and programmed cell death in cancer

Abstract

N6-methyladenosine (m6A) methylation, the most prevalent and abundant RNA modification in eukaryotes, has recently become a hot research topic. Several studies have indicated that m6A modification is dysregulated during the progression of multiple diseases, especially in cancer development. Programmed cell death (PCD) is an active and orderly method of cell death in the development of organisms, including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis. As the study of PCD has become increasingly profound, accumulating evidence has revealed the mutual regulation of m6A modification and PCD, and their interaction can further influence the sensitivity of cancer treatment. In this review, we summarize the recent advances in m6A modification and PCD in terms of their interplay and potential mechanisms, as well as cancer therapeutic resistance. Our study provides promising insights and future directions for the examination and treatment of cancers.

ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner

“…At the same time, the depletion of ABCA1 could elevate SQSTM1 expression, which indicated the repression of autophagy. Recent studies have shown that m 6 A modification mediates regulation of autophagy-related genes, affecting autophagy regulatory network and programmed cell death in multiple diseases 37 , 38 . Based on the results of our study and previous reports, we may reasonably speculate that the epigenetic modification of ABCA1 mediated by m 6 A demethylase ALKBH5 may affect tumor progression of SKCM via modulating cellular cholesterol homeostasis and autophagy.…”

FTO Sensitizes Oral Squamous Cell Carcinoma to Ferroptosis via Suppressing ACSL3 and GPX4

“…Given the significant role of m 6 A modification in tumor progression, there has been an increased focus on targeting m 6 A methylation and its associated proteins, such as FB23-2, a small molecule-targeting FTO in acute myeloid leukemia [46]. Numerous studies have underscored the crucial roles m 6 A methylation plays in drug resistance [47,48], radiotherapy tolerance [49,50], and programmed cell death [33,51].…”