29 m⁶A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset Analyses

Figure 3

Most m⁶A-RNA methylation regulators (m⁶A-RMRs) were downregulated in acute inflammatory diseases, suggesting that most m⁶A-RMRs are not required for the pathogenesis of acute inflammatory diseases. (a) The results showed that m⁶A-RMRs were downregulated (marked in blue) in sepsis and acute respiratory distress syndrome (ARDS), sepsis and shock, and severe trauma. (b) Venn diagram showed that in the same base disease, there were the shared upregulated or downregulated m⁶A regulators. There were five upregulated m⁶A-RMRs including shared writers WTAP and 19 downregulated regulators including nine shared genes in sepsis and ARDS of lung injury. There were six upregulated regulators including common writer PCIF1 and reader IGF2BP3 and 17 downregulated m⁶A methylation regulators (10 common genes) in sepsis and combined shock. WTAP was upregulated on the first day of sepsis and shock. In severe trauma, there were two genes upregulated and 15 genes downregulated including one common writer METTL3. In the three acute inflammatory diseases, nine downregulated m6A regulators (METTL3, RBM15, FTO, YTHDC2, HNRNPA2B1, EIF3A, HNRNPC, G3BP1, and CBLL1) were shared by three acute inflammation diseases. Note: the red marked genes are those that are up- or downregulated in different diseases. (c) 29 m⁶A-RMRs were examined in single-cell sequencing dataset online (https://singlecell.broadinstitute.org/single_cell) in an immune-cell signature of bacterial sepsis study (PMID: 32066974). The 11 out of 29 m⁶A methylation regulators including WTAP, ZC3H13, YTHDC1, YTHDF2, HNRNPA2B1, EIF3A, HNRNPC, RBMX, ELAVL1, G3BP1, and G3BP2 expressed differentially in different cell populations of bone-marrow under stimulation. (d) The expressions of most m⁶A methylation regulators except HNRNPA2B1 and HNRNPC were lower than those of others in PBMC subset cells (). Abbreviations: ARDS: acute respiratory distress syndrome; FC: fold change; NA: not available (missing value); NK: natural killer cell; GMP: granulocyte-macrophage progenitor; MEP: megakaryocyte-erythroid progenitors; MYL: myeloblasts; DC: dendritic cell; CMP: common myeloid progenitors; HSC/MPP: hematopoietic stem cells and multipotent progenitors; RBC: red blood cells; MS1: CD14⁺ cells with high expression of resistin (RETN), arachidonate 5-lipoxygenase activating protein (ALOX5AP), and interleukin-1 receptor type 2 (IL1R2); MS2: with high expression of class II major histocompatibility complex (MHC); MS3: similar to nonclassical CD16hi monocytes; MS4: which is composed of the remaining CD14⁺ cells that express low levels of both class II MHC and inflammatory cytokines; NHP: nonhuman primate; mTB: Mycobacterium tuberculosis; SHIV: simian-human immunodeficiency virus; CAF: cancer-associated fibroblasts.

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