Regulation of N6-Methyladenosine in the Differentiation of Cancer Stem Cells and Their Fate

Abstract

N6-methyladenosine (m6A) is one of the most common internal RNA modifications in eukaryotes. It is a dynamic and reversible process that requires an orchestrated participation of methyltransferase, demethylase, and methylated binding protein. m6A modification can affect RNA degradation, translation, and microRNA processing. m6A plays an important role in the regulation of various processes in living organisms. In addition to being involved in normal physiological processes such as sperm development, immunity, fat differentiation, cell development, and differentiation, it is also involved in tumor progression and stem cell differentiation. Curiously enough, cancer stem cells, a rare group of cells present in malignant tumors, retain the characteristics of stem cells and play an important role in the survival, proliferation, metastasis, and recurrence of cancers. Recently, studies demonstrated that m6A participates in the self-renewal and pluripotent regulation of these stem cells. However, considering that multiple targets of m6A are involved in different physiological processes, the exact role of m6A in cancer progression remains controversial. This article focuses on the mechanism of m6A and its effects on the differentiation of cancer stem cells, to provide a basis for elucidating the tumorigenesis mechanisms and exploring new potential therapeutic approaches.

N6-Methyladenosine-Regulated mRNAs: Potential Prognostic Biomarkers for Patients With Lung Adenocarcinoma

“…(A) Spearman correlation analysis and (B) co-expression network of m6A RNA methylation regulators, methyltransferases (METTL3, METTL14, METTL16, and WTAP), demethylases (FTO and ALKBH5) and 10 m6A-regulated mRNAs in the prognostic signature in TCGA LUAD patient cohorts. Xu et al, 2020). Notably, we observed that most genes with m6A methylation level changes were not accompanied by significant gene expression level changes.…”

The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

“…The sequence near the m6A modification site on the mRNA is highly conservative, mainly occurring on the adenine of the RRACH (R: purine; A: m 6 A; H: non-guanine) sequence, and its function is determined by the methyltransferase (writers: methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14) and WT1 associated protein (WTAP), et al), demethylase (erasers: fat mass and obesity associated protein (FTO) and alkB homologue 5 (ALKBH5), et al) and binding protein (readers: YTH domain containing family, the insulin like growth factor 2 mRNA binding protein (IGF2BP) family and heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1), et al) are jointly regulated ( Yang et al, 2018 ; Li M. et al, 2021 ). M 6 A modification is involved in a variety of biological processes, such as stem cell differentiation, cell division, gametogenesis and biological rhythms, et al, as well as the occurrence of a variety of diseases, including tumors, obesity and infertility ( Xu Y. et al, 2020 ; Zhang M. et al, 2020 ; Song et al, 2020 ). M 5 C modification is another prevalent RNA modification in multiple RNA species, including mRNAs, tRNAs, rRNAs, and ncRNAs ( Chen et al, 2021 ).…”

The Roles of RNA N6-Methyladenosine in Regulating Stem Cell Fate

“…Currently, inhibitors of FTO and ALKBH5 are being used as candidates for anticancer drug development, especially to inhibit the growth of CSCs by manipulating their m 6 A modification levels. Although these inhibitors have not been tested in clinical trials, they will provide more possibilities for the treatment of cancer (Xu et al, 2020).…”