Alterations in the pathways leading to the addition of the removal of the mA mark result in impaired gene expression and cellular function, which can lead to disease.
Normal mA levels are altered in a number of cancers. Reduced mA levels due to down regulation of METTL3 and/or METTL14 lead to the activation of a number of oncogenes, such as the gene encoding ADAM metallopeptidase domain 19 (ADAM19). Moreover, loss of mA also results in the down regulation of tumor suppressors like cyclin-dependent kinase inhibitor 2A (CDKN2A) and breast cancer 2 (BRCA2). On the other hand, increased mA levels inhibit tumor progression in certain types of cancer. In addition, single nucleotide polymorphisms (SNPs) on the gene encoding FTO have been associated with increased risk of breast and pancreatic cancer. Altered mA levels also contribute to hypoxia-induced enrichment of breast cancer stem cells phenotype. All things considered, "writers" and "erasers" of the mA mark may be good potential drug targets in cancer therapy.
Metabolic disorders are also affected by the mA mark due to the role of FTO. Overexpression of FTO results in increased body and fat mass, whereas loss of FTO leads to a reduction in lean body mass. However, the mechanisms by which changes in FTO expression affect body and fat mass are not understood.
Current research of the m6a epitranscriptome is continuing to uncover the implications of m6a and its post-physiological effects on ischemic stroke incidents. Microglial-mediated responses and contributing demethylases, including FTO and ALKBH5, appear to be a contributing factor for alterations of the cerebral m6a epitranscriptome. Mood disorders, such as major depressive disorder, have also been identified as disease processes associated with m6a epitranscriptome changes.