29 mA-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 mA-RNA methylation (epitranscriptomic) regulators (mA-RMRs) in 41 diseases and cancers and made significant findings: (1) a few mA-RMRs were upregulated; and most mA-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 mA-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated mA-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated mA-RMRs; end-stage renal failure (ESRF) downregulated 85% of mA-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated mA-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated mA-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated mA-RMRs were more than downregulated mA-RMRs in cancer types; five types of cancers upregulated ≥10 mA-RMRs; (8) proinflammatory M1 macrophages upregulated seven mA-RMRs; (9) 86% of mA-RMRs were differentially expressed in the six clusters of CD4Foxp3 immunosuppressive Treg, and 8 out of 12 Treg signatures regulated mA-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated mA-RMRs, and inhibition of CD40 upregulated mA-RMRs; (11) cytokines and interferons modulated mA-RMRs; (12) NF-B and JAK/STAT pathways upregulated more than downregulated mA-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated mA-RMRs; (14) mA writer RBM15 and one mA eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated mA-RMRs; and (15) 40 out of 165 ROS regulators were modulated by mA eraser FTO and two mA writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated mA-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.