Abstract
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.
Highlights
Adenosine methylation is the most common modification of RNA in eukaryotes
The connection between metabolism and tumorigenesis is attracting attention, and many gratifying results have revealed the link between the m6A modification and oncometabolite in cancer progression
The data demonstrates that the m6A modification regulators could act as promising candidates for diagnosis, prognosis, or treatment against cancer
Summary
Adenosine methylation is the most common modification of RNA in eukaryotes. The methyl group is attached to the nitrogen-6 position of adenosine, creating N6-methyladenosine or m6A (Wang et al, 2017). WTAP (a writer) promoted GC cell proliferation and glycolytic capacity and enhanced HK2 expression through m6A Methylation in Cancer Metabolism interacting with the m6A modified 3′-UTR of HK2 mRNA (Yu et al, 2021). The enhanced levels recruited the binding of YTHDF1, which promoted the translation of MYC mRNA and increased glycolysis and cancer progression (Yang et al, 2021). Guo and collaborators found that METTL3 depletion promoted the DEGS2 mRNA, increased DEGS2 expression in HCT116 cells, suggesting that METTL3 is essential for the stability and translation of DEGS2. YTHDF2 knockdown induced the level of DEGS2 mRNA expression, meaning that YTHDF2 contributes to the DEGS2 mRNA decay (Guo et al, 2021) This recent evidence suggests that m6A regulates lipid metabolism in cancer.
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