MiR-548a-3p Promotes Keratinocyte Proliferation Targeting PPP3R1 after Being Induced by IL-22

Psoriasis is an immune-mediated chronic skin disorder where T cells play a main role, and numerous inflammatory cytokines are implicated in its pathogenesis by initiating keratinocyte proliferation. Interleukin-22 (IL-22), an IL-10 family cytokines, is critical in the pathogenesis and development of psoriasis. To determine the target of microRNA (miR) -548a-3p and investigate its role in keratinocyte proliferation after treating human keratinocytes (HaCaT) with IL-22, we used quantitative reverse transcriptase PCR to measure the expression of miR-548a-3p in both HaCaT cells stimulated with IL-22 and psoriatic lesions, and then detected the biological function of miR-548a-3p in HaCaT cells by performing Counting Kit-8 (CCK-8) assays. Luciferase reporter assay was conducted to determine the target gene of miR-548a-3p. Immunohistochemistry and Western blot were performed to verify the target gene. Results showed that miR-548a-3p was significantly upregulated both in HaCaT cells treated with IL-22 and psoriatic lesions. The over expression of miR-548a-3p could promote the proliferation of HaCaT cells. Luciferase was mutated in the 3’UTR of PPP3R1, a gene coding Calcineurin. Immunohistochemistry and Western blot demonstrated that the expression of PPP3R1 decreased respectively in psoriatic lesions and HaCaT cells. In conclusion, the expression of miR-548a-3p is upregulated in IL-22 mediated keratinocyte proliferative disorder like psoriasis. The impact of miR-548a-3p on keratinocyte proliferation may be implemented by targeting PPP3R1 and T regulatory cells may be involved in the pathogenesis of psoriasis.