N6 -methyladenosine Steers RNA Metabolism and Regulation in Cancer.

Abstract

As one of the most studied ribonucleic acid (RNA) modifications in eukaryotes, N6‐methyladenosine (m6A) 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 m6A epigenetic marks, respectively, shape the cellular m6A landscape, while reader proteins preferentially recognize m6A 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 m6A regulators. Aberrant expression of m6A regulators has been widely reported in various types of cancer, leading to cancer initiation, progression, and drug resistance. The close links between m6A and cancer shed light on the potential use of m6A methylation and its regulators as prognostic biomarkers and drug targets for cancer therapy. Given the notable effects of m6A in reversing chemoresistance and enhancing immune therapy, it is a promising target for combined therapy. Herein, we summarize the recent discoveries on m6A and its regulators, emphasizing their influences on RNA metabolism, their dysregulation and impacts in diverse malignancies, and discuss the clinical implications of m6A modification in cancer.