N^(6)-methyladenosine Steers RNA Metabolism and Regulation in Cancer

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.