Intertwined regulation between RNA m6A modification and cancer metabolism

Abstract

RNA N6-methyladenosine (m⁶A) has been identified as the most common, abundant and conserved internal modification in RNA transcripts, especially within eukaryotic messenger RNAs (mRNAs). Accumulating evidence demonstrates that RNA m⁶A modification exploits a wide range of regulatory mechanisms to control gene expression in pathophysiological processes including cancer. Metabolic reprogramming has been widely recognized as a hallmark of cancer. Cancer cells obtain metabolic adaptation through a variety of endogenous and exogenous signaling pathways to promote cell growth and survival in the microenvironment with limited nutrient supply. Recent emerging evidence reveals reciprocal regulation between the m⁶A modification and disordered metabolic events in cancer cells, adding more complexity in the cellular network of metabolic rewiring. In this review, we summarize the most recent advances of how RNA methylation affects tumor metabolism and the feedback regulation of m⁶A modification by metabolic intermediates. We aim to highlight the important connection between RNA m⁶A modification and cancer metabolism, and expect that studise of RNA m⁶A and metabolic reprogramming will lead to greater understanding of cancer pathology.