Department of Dermatology, Qilu Hospital, Shandong University, 107 Wenhua W Rd, Jinan, 250012, China.
Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
Inflammation. 2018 Dec;41(6):2160-2170. doi: 10.1007/s10753-018-0859-7.
We investigated the molecular mechanisms underlying the role of miRNAs in the pathogenesis of psoriasis to discover novel potential diagnostic markers and treatment targets. We screened Chinese Han individuals using gene chip technology to identify differentially expressed miRNAs in the epidermal tissue of lesions from patients with psoriasis versus that from healthy controls. We also used bioinformatics methods and molecular biology experiments to predict and verify target genes and signaling pathways that may have an underlying role in normal human epidermal keratinocyte (NHEK) proliferation. Differentially expressed miRNAs were found in the epidermal tissue of lesions from patients with psoriasis; 45 were upregulated, and 71 were downregulated. Among them, miR-320b was significantly downregulated. Low miR-320b expression levels in NHEKs promoted cell proliferation. The luciferase assay results showed that AKT3 is a target gene of miR-320b. The protein phosphorylation levels of STAT3 and SAPK/JNK in the intracellular signaling pathway were significantly upregulated by miR-320b downregulation. Our findings indicate that miR-320b negatively regulates NHEK proliferation by targeting AKT3 to regulate the STAT3 and SAPK/JNK signaling pathways and might participate in the pathogenesis of psoriasis in Chinese Han populations. miR-320b may also be a novel diagnostic marker or therapeutic target for this disease.
我们研究了 miRNA 在银屑病发病机制中的作用的分子机制，以发现新的潜在诊断标志物和治疗靶点。我们使用基因芯片技术筛选中国汉族个体，以鉴定银屑病患者皮损表皮组织中与健康对照组相比差异表达的 miRNA。我们还使用生物信息学方法和分子生物学实验来预测和验证可能在正常人类表皮角质形成细胞（NHEK）增殖中起作用的靶基因和信号通路。在银屑病患者皮损表皮组织中发现差异表达的 miRNA；45 个上调，71 个下调。其中，miR-320b 显著下调。NHEK 中 miR-320b 表达水平低可促进细胞增殖。荧光素酶检测结果表明，AKT3 是 miR-320b 的靶基因。miR-320b 下调可显著上调细胞内信号通路中 STAT3 和 SAPK/JNK 的蛋白磷酸化水平。我们的研究结果表明，miR-320b 通过靶向 AKT3 负调控 NHEK 增殖，调节 STAT3 和 SAPK/JNK 信号通路，可能参与中国汉族人群银屑病的发病机制。miR-320b 也可能是该疾病的一种新的诊断标志物或治疗靶点。
