Interleukin-17 regulates keratinocyte proliferation in psoriasis through the MALAT1/miR-125b/ BRD4 axis

Abstract

Background: Psoriasis is a common chronic inflammatory dermatosis characterized by scaly erythema and plaques. This study explored the specific mechanism of LncRNA MALAT1 in the occurrence and development of psoriasis. Methods: We collected serum from psoriasis patients and healthy subjects and measured the expression of IL-17 in serum by ELISA. HaCaT cells were stimulated with 80 ng/mL IL-17 and simultaneously transfected with shMALAT1 or were treated with Secukinumab (anti-IL-17A). The CCK-8 and EdU experiments were used to detect cell viability and proliferation, flow cytometry showed the level of cell cyle, and corresponding cyclins were measured by WB and RT-QPCR, and changes in a series of LncRNAs were detected. A luciferase activity analysis and ChIP assay verified the targeting relationship between MALAT1 and p65. Results: IL-17 treatment of HaCaT cells promoted cell proliferation and increased MALAT1 expression. The binding of p65 to the promoter of MALAT1 promoted keratinocyte proliferation. The proliferation of HaCaT cells induced by IL-17 was repressed by Secukinumab. The expression of miR-125b was notably reduced in cells treated with IL-17, whereas Secukinumab rescued the expression of miR-125b. IL-17 treatment resulted in elevated BRD4 expression, which was attenuated by Secukinumab. Conclusions: IL-17 stimulates HaCaT cell proliferation by inducing high expression of MALAT1, and p65 binds to the promoter of MALAT1 to promote its expression, which may provide a novel direction for the treatment of psoriasis.