Interplay Between m⁶A RNA Methylation and Regulation of Metabolism in Cancer

Methylation of adenosine in RNA to N6-methyladenosine (m⁶A) is widespread in eukaryotic cells with his integral RNA regulation. This dynamic process is regulated by methylases (editors/writers), demethylases (remover/erasers), and proteins that recognize methylation (effectors/readers). It is now evident that m⁶A is involved in the proliferation and metastasis of cancer cells, for instance, altering cancer cell metabolism. Thus, determining how m⁶A dysregulates metabolic pathways could provide potential targets for cancer therapy or early diagnosis. This review focuses on the link between the m⁶A modification and the reprogramming of metabolism in cancer. We hypothesize that m⁶A modification could dysregulate the expression of glucose, lipid, amino acid metabolism, and other metabolites or building blocks of cells by adaptation to the hypoxic tumor microenvironment, an increase in glycolysis, mitochondrial dysfunction, and abnormal expression of metabolic enzymes, metabolic receptors, transcription factors as well as oncogenic signaling pathways in both hematological malignancies and solid tumors. These metabolism abnormalities caused by m⁶A's modification may affect the metabolic reprogramming of cancer cells and then increase cell proliferation, tumor initiation, and metastasis. We conclude that focusing on m⁶A could provide new directions in searching for novel therapeutic and diagnostic targets for the early detection and treatment of many cancers.