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.
KEY WORDSpsoriasis IL-22 miR-548a-3p PPP3R1
We deeply appreciate all psoriasis patients and control subjects for their participation.
This project was funded by the National Natural Science Foundation of China (81573046).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
The research was approved by the Ethics Committee of Shandong University, China, and was accordant with the 1964 Helsinki Declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.
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