Transcriptome-Wide m(6)A Methylation in Skin Lesions From Patients With Psoriasis Vulgaris

N(6)-methyladenosine (m(6)A) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed m(6)A transcriptome-wide profiling in three kinds of skin tissue: involved psoriatic skin (PP), uninvolved psoriatic skin (PN), and healthy control skin samples (NN). The findings revealed that transcripts of PP contained the fewest m(6)A peaks and lowest m(6)A peak density. The greatest differences of m(6)A methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated m(6)A was mainly enriched within the CDSs and 3′UTRs, while hypomethylated m(6)A was not only enriched within CDSs and 3′UTRs, but also within 5′UTRs. GO and KEGG pathway analyses indicated that hypermethylated transcripts in PP were particularly associated with response-associated terms, cytokine production, and olfactory transduction. Meanwhile, hypomethylated transcripts in PP were mainly associated with development-related processes and the Wnt signaling pathway. In addition, we discovered that 19.3–48.4% of the differentially expressed transcripts in psoriasis vulgaris were modified by m(6)A, and that transcripts with lower expression were more preferentially modified by m(6)A. Moreover, upregulation of gene expression was often accompanied by upregulation of m(6)A methylation, suggesting a regulatory role of m(6)A in psoriasis vulgaris gene expression.