新疆哈萨克族、维吾尔族原发性高血压lncRNA的差异表达及其机制研究

The prevalence of hypertension in the Kazakh population is significantly higher than the Uygur in Xinjiang. In recent years, research results suggest that long non-coding RNA (lncRNA) expression or dysfunction is closely related to human disease. To explore the role of lncRNA in Kazakh, Uygur EH pathogenesis, the subject intends to study comparative difference lncRNA and their associated mRNA expression profiles between Kazakh, Uygur EH patients and controls. Screening lncRNA can be used as ethnic molecular markers. The method of bioinformatics is able to annotate the differentially expressed mRNA function and signaling pathways involved. It can be screened the EH-related mRNA. We will construct the regulation networks of lncRNA-mRNA co-expression by binding lncRNA expression profiles and study on lncRNA its regulation of target gene mRNA expression. It may clarify the lncRNA regulatory networks in Kazakh, Uygur EH and will provide the basis for revealing the pathogenesis of EH and the molecular targets for individualized treatment in Kazakh and Uygur from Xinjiang.

新疆地区哈萨克族是一高血压高发民族，其患病率明显高于同地区维吾尔族。近年来研究提示，长链非编码RNA（lncRNA）的表达或功能异常与人类疾病的发生密切相关。然而lncRNA在原发性高血压（EH）中的作用目前依然不清楚。为探讨lncRNA在新疆哈萨克族、维吾尔族EH发病机制中的作用，本课题拟对比研究新疆哈萨克族、维吾尔族EH患者与对照组之间lncRNA及其相关mRNA表达谱的差异，筛选出能作为两民族分子标记物的lncRNA。运用生物信息学方法注释差异表达的mRNA的功能及所涉及的信号通路，筛选出与EH发病相关的mRNA，结合lncRNA差异表达谱，构建lncRNA-mRNA共表达调控网络，研究lncRNA对其靶mRNA表达的调控作用，阐明lncRNA 及其调控网络与新疆哈萨克族、维吾尔族EH 发生发展的关系，为揭示新疆哈萨克族、维吾尔族EH的发病机制及个体化治疗分子靶点的筛选提供依据。

越来越多的证据表明，非编码RNA（ncRNA）有助于阐明心血管疾病的发病机理。但是，它们在原发性高血压（EH）中的作用仍不清楚。因此，我们从高风险人群中鉴定了EH患者中差异表达的长非编码RNA（lncRNA）和环状RNA（circRNA），并构建了竞争性内源RNA调控网络，该网络预测了特定lncRNA/circRNA-microRNA-mRNA之间潜在的诊断和治疗意义。我们的分析确定了两个lncRNAs，跨膜蛋白183A假基因（LOC646616）和亮氨酸氨基肽酶3假基因2（LAP3P2），以及两个circRNA，hsa_circ_0039388和hsa_circ_0038648，它们与无翼型MMTV整合位点家族成员3（WNT3）高度共表达。钙/钙调蛋白依赖性蛋白激酶II抑制剂2（CAMK2N2）mRNA，亦与这两个转录本共享共同的microRNA结合位点。我们还证实，由LOC646616/microRNA-637/WNT3组成的相互调节的网络可控制WNT3的表达并影响体外人动脉平滑肌细胞的活力和侵袭性。这些发现突显了一种新型的基于ncRNA的调控机制，可能在EH中驱动WNT /β-catenin激活，并表明所鉴定的ncRNA可作为EH的生物标记物和治疗靶标。