Psoriasis is a common immune-mediated chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation, differentiation and apoptosis. However, the exact etiology and pathogenesis are still unclear. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. It has been demonstrated that Interleukin-22 (IL-22) plays vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. The aim of our study was to explore the possible functional role of miR-20a-3p in psoriasis and in IL-22 induced keratinocyte proliferation. Here, we found that miR-20a-3p was down-regulated in psoriatic lesions and in HaCaT cells (human keratinocyte cell line) treated by IL-22 stimulation. Functional experiments showed that overexpression of miR-20a-3p in HaCaT cells suppressed proliferation and induced apoptosis while its knockdown promoted cell proliferation and reduces cell apoptosis. Mechanistically, SFMBT1 was identified as the direct target of miR-20a-3p by dual luciferase reporter assay. SFMBT1 knockdown was demonstrated to inhibit cell growth and induced apoptosis, which was consistent with the function of miR-20a-3p upregulation in HaCaT cells. In addition, results of western blot analysis showed that miR-20a-3p upregulation or SFMBT1 knockdown changed the protein expression levels of TGF-β1 and survivin. Our findings suggest that miR-20a-3p play roles through targeting SFMBT1 and TGF-β1/Survivin pathway in HaCaT cells, and loss of miR-20a-3p in psoriasis may contribute to hyperproliferation and aberrant apoptosis of keratinocytes.

银屑病是一种常见的免疫介导的慢性炎症性皮肤病，其特征是角质形成细胞异常增殖、分化和凋亡。然而，确切的病因和发病机制仍不清楚。关于 microRNA 在牛皮癣中的作用的证据正在迅速积累。已证明，白细胞介素 22 (IL-22) 通过与牛皮癣发病机制中的角质形成细胞相互作用，在 T 细胞介导的免疫反应中发挥重要作用。我们研究的目的是探讨 miR-20a-3p 在银屑病和 IL-22 诱导的角质形成细胞增殖中可能的功能作用。在这里，我们发现 miR-20a-3p 在银屑病皮损和经 IL-22 刺激处理的 HaCaT 细胞（人角质形成细胞系）中下调。功能实验表明，HaCaT细胞中miR-20a-3p的过表达抑制增殖并诱导细胞凋亡，而其敲低则促进细胞增殖并减少细胞凋亡。从机制上讲，双荧光素酶报告基因检测将 SFMBT1 确定为 miR-20a-3p 的直接靶标。 SFMBT1 敲低被证明可以抑制细胞生长并诱导细胞凋亡，这与 HaCaT 细胞中 miR-20a-3p 上调的功能一致。此外，蛋白质印迹分析结果显示，miR-20a-3p上调或SFMBT1敲低改变了TGF-β1和survivin的蛋白表达水平。我们的研究结果表明，HaCaT 细胞中 miR-20a-3p 通过靶向 SFMBT1 和 TGF-β1/Survivin 通路发挥作用，牛皮癣中 miR-20a-3p 的缺失可能导致角质形成细胞过度增殖和异常凋亡。