The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

Abstract

The m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

Increased METTL3-mediated m6A methylation inhibits embryo implantation by repressing HOXA10 expression in recurrent implantation failure

“…Meanwhile, m 6 A modification can be removed by “erasers” demethylase, such as fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5). In addition, m 6 A “readers” are responsible for recognition of the m 6 A modification [ 22 ]. Members of every classes of m 6 A regulators cooperatively participate in the regulation of mRNA stability and translation, affect gene expression output and thus play an important role in physiological and pathological conditions [ 22 – 26 ].…”

m6A Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Pancreatic Cancer

“…A growing body of evidence shows that m 6 A regulators are involved in vital biological processes and are dynamically regulated in many physiological and pathological processes (7)(8)(9). Abnormal expression and genetic alterations of m 6 A regulators are closely related to events such as developmental defects, metabolic disorders, abnormal immune regulation, and tumor progression (10,11). A comprehensive understanding of potential m 6 A regulators' expression perturbation and genetic variation under cancer heterogeneity will facilitate the identification of therapeutic targets based on RNA methylation (12,13).…”

m6A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

“…Recently, m 6 A, an important epigenetic modification of RNA, has caused a growing worldwide concern, as it is reported to be associated with mRNA stability, translation, subcellular localization, and alternative splicing [16,17,30]. Currently, the accumulated evidence shows that m 6 A modification can regulate various of cellular biological processes including autophagy and metabolite synthesis [31,32]. However, the dysregulation of autophagy mediated by m 6 A may result in the occurrence of some diseases, even cancers.…”