RBM15-Mediated m6A Modification of K17 Affects Keratinocytes Response to IL-17A Stimulation in Psoriasis.

Objective: Psoriasis is characterized by excessive proliferation and abnormal differentiation of epidermal keratinocytes. This study aimed to reveal the function and mechanism of a N6-methyladenosine (m6A) methyltransferase RNA-binding motif protein 15 (RBM15) in IL-17A-induced keratinocytes.

Methods: A immortalized keratinocyte cell line HaCaT was used to undergo the IL-17A stimulation. The mRNA levels were detected by qRT-PCR, whereas the protein levels were measured by western blotting. The change of keratinocytes proliferation was determined using CCK8 and EdU assays, and the inflammation factors (IL-8 and TNF-α) in keratinocytes were analyzed by qRT-PCR. The m6A modification of Keratin 17 (K17) was confirmed by MeRIP and mRNA stability assays.

Results: The levels of RBM15 and K17 in skin samples from patients with psoriasis and IL-17A-induced keratinocytes were upregulated, and showed the positive correlation. Silencing RBM15 suppressed viability, proliferation, and inflammation of keratinocytes that were enhanced by IL-17A stimulation. Moreover, RBM15 knockdown reduced the stability of K17 mRNA via m6A modification method. Since K17 is modified by RBM15, its overexpression relieved the effects of RBM15 knockdown on keratinocytes under IL-17A stimulation.

Conclusion: This study revealed that RBM15 knockdown suppressed proliferation and inflammation by mediating m6A modification of K17 to reduce K17 stability in IL-17A-induced keratinocytes. Our findings may provide novel idea for improving the treatment of psoriasis.