RNA Modifications in Cancer Metabolism and Tumor Microenvironment

Abstract

RNA modifications have recently been recognized as essential posttranscriptional regulators of gene expression in eukaryotes. Investigations over the past decade have revealed that RNA chemical modifications have profound effects on tumor initiation, progression, refractory, and recurrence. Tumor cells are notorious for their robust plasticity in response to the stressful microenvironment and undergo metabolic adaptations to sustain rapid cell proliferation, which is termed as metabolic reprogramming. Meanwhile, cancer-associated metabolic reprogramming leads to substantial alterations of intracellular and extracellular metabolites, which further reshapes the tumor microenvironment (TME). Moreover, cancer cells compete with tumor-infiltrating immune cells for the limited nutrients to maintain their proliferation and function in the TME. In this chapter, we review recent interesting findings on the engagement of epitranscriptomic pathways, especially the ones associated with N⁶-methyladenosine (m⁶A), in the regulation of cancer metabolism and the surrounding microenvironment. We also discuss the promising therapeutic approaches targeting RNA modifications for anti-tumor therapy.

Keywords: Aerobic glycolysis; Amino acid metabolism; Cancer metabolism; Immune cells; Immunotherapy; Lipid metabolism; RNA modification; Tumor microenvironment; m6A.