非编码RNA在银屑病中扮演着重要角色。申请者通过分析深度测序的银屑病miRNAs数据库，发现并验证了miR-187在5种炎症因子刺激的角质形成细胞中都显著下调。过表达miR-187能明显抑制银屑病角质形成细胞增殖并促进其凋亡。而且miR-187的下调与其互补配对的长非编码RNA KCNQ1OT1相关。抑制KCNQ1OT1能逆转炎症因子诱导的miR-187下调。为了进一步确证KCNQ1OT1-miR-187信号轴的存在以及它在银屑病中的作用，本项目拟通过qPCR及报告基因等方法探索KCNQ1OT1对miR-187的调控作用；通过萤光报告基因等方法探讨miR-187抑制银屑病角质形成细胞增殖，促进其凋亡的机制；在银屑病整体动物模型上验证该调控轴的作用及干预后的治疗作用；以及在病理组织上检测该调控轴的变化。本项目的完成有望为银屑病的发病机制提供新认识，也将为其诊断和治疗提供新标记物和新靶点。

Noncoding RNA plays an important role in psoriasis. Previously, we analyze and verify the deep sequencing of psoriasis miRNAome from human skin. We find that miR-187 is down-regulation in the IL-6/IL-17A/IL-22/IL-1β/TNFα stimulated psoriatic keratinocytes (KCs). Over-expression of miR-187 inhibits psoriatic KCs proliferation and induces apoptosis. These results strongly suggest that down-regulation of miR-187 is involved in the pathology of psoriasis. Furthermore, we find that long non-coding RNA KCNQ1OT1, which is complementary to miR-187, is up-regulated in the cytokines-stimulated psoriatic KCs. In addition, silence of KCNQ1OT1 can reverse the cytokines induced down-regulation of miR-187. To further detect the role of negative regulation of miR-187 by KCNQ1OT1 in psoriasis, RNA Immuno-precipitation will be used to explore the regulatory molecular mechanism of KCNQ1OT1-miR-187 signal axis. And then, we use microRNAs targets databases and luciferase to investigate the targets of miR-187. Furthermore, KCNQ1OT1 overexpression shRNA or silencer, as well as miR-187 antagomir or agomir, will be applied to psoriatic animal model to determine the contributory role and the therapeutic potential of KCNQ1OT1-miR-187 signal axis. At last, we use the qPCR and hybridization in situ to explore the relationship between KCNQ1OT1-miR-187 signal axis and psoriasis. We believe that this program will help us to reveal new psoriatic pathogenic evidence from epigenetics perspective, and may also provide new diagnostic markers and therapeutic targets for psoriasis.