Department of Dermatology, Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Exp Dermatol. 2021 Jul;30(7):932-942. doi: 10.1111/exd.14188. Epub 2020 Sep 20.
Psoriasis is a chronic inflammatory disease characterized by abnormal hyperproliferation and differentiation. The object of this study is to explore the role of microRNA-215-5p in psoriasis-like inflammation. The expression of miR-215-5p was found to be down-regulated in pro-inflammatory factor-stimulated HaCaT cells and imiquimod (IMQ)-treated skin tissues. Overexpression of miR-215-5p suppressed the proliferation and cell cycle progression of HaCaT cells. Further, miR-215-5p agomir alleviated the disease severity, pathological features and Ki67 positive cells in IMQ-treated mice. Luciferase assay confirmed that miR-215-5p could bind to the 3'UTR of DYRK1A. The in vitro and in vivo results showed that miR-215-5p negatively regulates DYRK1A, which further inhibited EGFR and its downstream signalling pathways, AKT and ERK. Collectively, our results provide evidence that overexpression of miR-215-5p inhibits the proliferation of HaCaT cells and alleviates psoriasis-like inflammation partly by DYRK1A mediated inhibition of the EGFR signalling pathway. miR-215-5p may serve as a novel small molecule for therapeutic intervention in psoriasis.
银屑病是一种慢性炎症性疾病，其特征为异常的过度增殖和分化。本研究旨在探讨 microRNA-215-5p 在银屑病样炎症中的作用。研究发现，促炎因子刺激的 HaCaT 细胞和咪喹莫特（IMQ）处理的皮肤组织中 miR-215-5p 的表达下调。miR-215-5p 的过表达抑制了 HaCaT 细胞的增殖和细胞周期进程。此外，miR-215-5p agomir 减轻了 IMQ 处理小鼠的疾病严重程度、病理特征和 Ki67 阳性细胞。荧光素酶报告基因实验证实 miR-215-5p 可以与 DYRK1A 的 3'UTR 结合。体外和体内结果表明，miR-215-5p 负调控 DYRK1A，进而抑制 EGFR 及其下游信号通路、AKT 和 ERK。综上所述，我们的研究结果表明，miR-215-5p 的过表达通过 DYRK1A 介导的 EGFR 信号通路抑制抑制 HaCaT 细胞的增殖，从而部分缓解银屑病样炎症。miR-215-5p 可能成为治疗银屑病的新型小分子药物。
