N⁶‐methyladenosine Steers RNA Metabolism and Regulation in Cancer

Abstract

As one of the most studied ribonucleic acid (RNA) modifications in eukaryotes, N 6 -methyladenosine (m 6 A) has been shown to play a predominant role in controlling gene expression and influence physiological and pathological processes such as oncogenesis and tumor progression. Writer and eraser proteins, acting opposite to deposit and remove m 6 A epigenetic marks, respectively, shape the cellular m 6 A landscape, while reader proteins preferentially recognize m 6 A modifications and mediate fate decision of the methylated RNAs, including RNA synthesis, splicing, exportation, translation, and stability. Therefore, RNA metabolism in cells is greatly influenced by these three classes of m 6 A regulators. Aberrant expression of m 6 A regulators has been widely reported in various types of cancer, leading to cancer initiation, progression, and drug resistance. The close links between m 6 A and cancer shed light on the potential use of m 6 A methylation and its regulators as prognostic biomarkers and drug targets for cancer therapy. Given the notable effects of m 6 A in reversing chemoresistance and enhancing immune therapy, it is a promising target for combined therapy.Herein, we summarize the recent discoveries on m 6 A and its regulators, emphasizing their influences on RNA metabolism, their dysregulation and impacts in diverse malignancies, and discuss the clinical implications of m 6 A modification in cancer.

Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning

“…As one of the most important RNA modifications, m6A is involved in regulating gene expression and physiological and pathological processes, such as tumor development and progression ( Dong et al, 2021 ; Garbo et al, 2021 ; Han et al, 2021 ). Furthermore, m6A regulators play an important role in lung cancer progression, for example FTOH and ALKBH5 have been shown to promote the proliferation of lung cancer cells, and YTHDF2 can regulate tumor metabolism ( Khan and Malla, 2021 ; Xu F. et al, 2021 ; Xu R. et al, 2021 ).…”

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

“…Effective biomarkers and assays with high sensitivity and specificity should greatly improve the efficiency of early tumor diagnosis. m 6 A methylation and its regulators are emerging biomarkers for tumor diagnosis and prognosis [ 266 , 267 ]. Due to their metabolic reversibility, high abundance and stability, methylated nucleosides can be obtained in biological fluids or circulating cells [ 268 , 269 ].…”

An Interplay between Epigenetics and Translation in Oocyte Maturation and Embryo Development: Assisted Reproduction Perspective

“…METTL3 was found to play a role in folliculogenesis, ovulation, maintenance of DNA integrity, and preimplantation development [153]. The same enzyme is engaged in the angiogenesis of atherosclerotic mouse model embryos by upregulating vascular-endothelial growth factor (VEGF) [154] through m 6 A [155]. In zebrafish embryos, METTL3 regulated PHLPP2/mTOR-AKT signalling [156].…”