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

Figure 4

More m⁶A-RNA methylation regulators (m⁶A-RMRs) upregulated in type 2 diabetes and abnormal lipid metabolism than in obesity and obesity-related diseases. (a) The result showed that the majority m⁶A-RMRs were downregulated (marked in blue) in obesity and obesity-related diseases, and only the expression fold change of IGF2BP1 and IGF2BP3 are above two. The expression pattern of m⁶A-RMRs in different tissues of T2D and atherosclerosis disease is different. (b) Venn diagram showed that in obesity, the decreased genes are more than the increased genes (six and 15, respectively); in T2D, few genes are shared in different tissues; in atherosclerosis disease, PCIF and PRRC2A are commonly upregulated and METTL14 is commonly downregulated in macrophages and monocytes. In the three metabolic diseases, the majority m⁶A-RMRs showed the heterogeneity expression (genes marked in red). METTL14 is the common decreased m⁶A methylation regulator among obesity, T2D, and atherosclerosis diseases. Note: the red marked genes are those that are up- or downregulated in different diseases. Expression of m⁶A-RMRs is different in cell populations of atherosclerosis study. 29 RNA m⁶A-RMRs were examined in single-cell sequencing dataset online (https://singlecell.broadinstitute.org/single_cell) in atherosclerotic mice (PMID: 30830865). The results showed that expressions of Wtap, Pcif1, Alkbh5, Ythdc1, Ythdf1, Ythdf2, Ythdf3, Hnrnpa2b1, Eif3a, Fmr1, Hnrnpc, Prrc2a, G3bp1, and G3bp2 were decreased in progressive atherosclerosis compared with regression atherosclerosis. The expression of Elavl1 was increased in progressive atherosclerosis compared with regression atherosclerosis (Virma, Igf2bp1 not found) (). Abbreviations: FC: fold change; T2D: type 2 diabetes; MUO: metabolically unhealthy obese; FCH: familial combined hyperlipidemia; FHC: familial hypercholesterolemia; NA: not available (missing value).

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