Interplay Between m6A RNA Methylation and Regulation of Metabolism in Cancer

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.

N6-Methyladenosine Modification Patterns and Tumor Microenvironment Immune Characteristics Associated With Clinical Prognosis Analysis in Stomach Adenocarcinoma

“…We retrieved the literature related to m6A methylation modification, and a total of 23 acknowledged m6A regulator genes were curated and analyzed to identify distinct m6A methylation modification patterns ( Chen et al, 2019 ; Zaccara et al, 2019 ; Liu et al, 2022 ; Mobet et al, 2022 ). Based on the mRNA expression data available in TCGA, we analyzed 23 m6A RNA methylation regulators (METTL3, METTL14, METTL16, WTAP, VIRMA, ZC3H13, RBM15) RBM15B, FTO, ALKBH5, YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, HNRNPC, FMR1, LRPPRC, IGF2BP1, IGF2BP2, IGF2BP3, HNRNPA2B1, and RBMX) data.…”

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

“…Further, the expression of HIF-1α and the activity of HIF pathway can also be upregulated by DNA methylation in cancer [ 112 ]. At the RNA level, N6-methyladenosine (m6A) modifications of RNAs take part in RNA metabolism to regulate the level of mRNA [ 114 ]. In CRC, METTL3 mediates the m6A modification of HK2 and SLC2A1 mRNA, which leads to their stabilization and activates the glycolytic pathway [ 115 ].…”

Research Progress of RNA Methylation Modification in Colorectal Cancer

“…Epigenetic modifications are dynamically reversible and heritable, including DNA methylation, histone modifications, chromatin remodeling, microRNAs (miRNAs) and noncoding RNAs (ncRNAs) which are of great importance in the progression and metastasis of colorectal cancer ( Huang et al, 2021a ). Recently, major breakthroughs have been made in the research on DNA omics and proteomics in the occurrence and development of tumors, and the epigenetic modification at the RNA level has also attracted the attention of many researchers ( Skvortsova et al, 2019 ; Sivanand and Vander Heiden, 2020 ; Mobet et al, 2022 ; Wishart, 2022 ).…”