Transcriptome-Wide m⁶A Methylation in Skin Lesions From Patients With Psoriasis Vulgaris

N⁶-methyladenosine (m⁶A) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed m⁶A 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 m⁶A peaks and lowest m⁶A peak density. The greatest differences of m⁶A methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated m⁶A was mainly enriched within the CDSs and 3'UTRs, while hypomethylated m⁶A 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 m⁶A, and that transcripts with lower expression were more preferentially modified by m⁶A. Moreover, upregulation of gene expression was often accompanied by upregulation of m⁶A methylation, suggesting a regulatory role of m⁶A in psoriasis vulgaris gene expression.