miR-320b Is Down-Regulated in Psoriasis and Modulates Keratinocyte Proliferation by Targeting AKT3
miR-320b Is Down-Regulated in Psoriasis and Modulates Keratinocyte Proliferation by Targeting AKT3
复制标题
miR-320b 在银屑病中下调并通过靶向 AKT3 调节角质形成细胞增殖
DOI：
10.1007/s10753-018-0859-7
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发表时间：
2018-12-01
期刊：
影响因子：
5.1
通讯作者：
Sun, Qing
中科院分区：
文献类型：
--
作者：
Wang, Yan;Yu, Xiaojing;Sun, Qing
摘要我们研究了mirna在银屑病发病机制中的分子机制，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患者，以鉴定银屑病患者与健康对照者病变表皮组织中差异表达的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）增殖中起潜在作用的靶基因和信号通路。银屑病患者皮损表皮组织中存在差异表达的mirna；45个上调，71个下调。其中，miR-320b显著下调。NHEKs中miR-320b的低表达水平促进细胞增殖。荧光素酶检测结果显示AKT3是miR-320b的靶基因。miR-320b下调后，细胞内信号通路中STAT3和SAPK/JNK蛋白磷酸化水平显著上调。我们的研究结果表明，miR-320b通过靶向AKT3调控STAT3和SAPK/JNK信号通路负向调控NHEK增殖，可能参与了中国汉族人群银屑病的发病机制。miR-320b也可能成为该病新的诊断标记物或治疗靶点。
AbstractWe 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 psoriasisversusthat 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.