29 m(6)A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset Analyses

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m(6)A-RNA methylation (epitranscriptomic) regulators (m(6)A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m(6)A-RMRs were upregulated; and most m(6)A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m(6)A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m(6)A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m(6)A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m(6)A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m(6)A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m(6)A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m(6)A-RMRs were more than downregulated m(6)A-RMRs in cancer types; five types of cancers upregulated ≥10 m(6)A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m(6)A-RMRs; (9) 86% of m(6)A-RMRs were differentially expressed in the six clusters of CD4(+)Foxp3(+) immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m(6)A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m(6)A-RMRs, and inhibition of CD40 upregulated m(6)A-RMRs; (11) cytokines and interferons modulated m(6)A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m(6)A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m(6)A-RMRs; (14) m(6)A writer RBM15 and one m(6)A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m(6)A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m(6)A eraser FTO and two m(6)A writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated m(6)A-RMRs in 41 diseases and cancers, nine cellular and molecular mechanisms, novel therapeutic targets for inflammatory disorders, metabolic cardiovascular diseases, autoimmune diseases, organ failures, and cancers.