长链非编码RNA-MALAT1在缺氧肺动脉平滑肌细胞增殖中的作用及分子机制的研究

项目名称： 长链非编码RNA-MALAT1在缺氧肺动脉平滑肌细胞增殖中的作用及分子机制的研究

项目编号： No.31500936

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 郑晓东

作者单位： 哈尔滨医科大学

项目金额： 20万元

中文摘要： 缺氧引起肺动脉平滑肌细胞（PASMCs）增殖是缺氧肺动脉高压的重要特征，但其分子机制仍不明确。长链非编码 RNA(lncRNA)可在表观遗传学、转录及转录后水平等多层面调控基因的表达，其功能多样性涉及和细胞增殖有关的诸多环节，但是否参与缺氧PASMCs增殖尚不清楚。我们的结果提示缺氧升高lncRNA-MALAT1表达，MALAT1参与调控PASMCs增殖相关蛋白的表达。提示缺氧可能通过MALAT1调控和增殖有关的分子及信号转导系统，引起PASMCs增殖。拟通过下述研究证明该假设：(1)肺动脉高压患者和小鼠模型的MALAT1表达及组织细胞分布特点；(2) MALAT1在缺氧PASMCs增殖中的作用和作用的具体环节；(3)MALAT1通过microRNAs，靶蛋白及蛋白质互作网络调控增殖的分子机制。研究结果将首次阐明MALAT1调控PASMCs增殖的新机制，为肺动脉高压提供治疗和药物研究靶点。

中文关键词： 肺血管平滑肌细胞；肺动脉高压；增殖；长链非编码RNA；肺腺癌转移相关转录因子1

英文摘要： The most significant characterize of hypoxic pulmonary hypertension is the proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism of hypoxia-induced PASMCs proliferation remains unclear. Long non-coding RNA (lncRNA) plays an important role in regulation of gene expression in epigenetic, transcriptional and post-transcriptional level, the diversity functions involves in most aspects of proliferation signaling, however, whereas lncRNA involves in hypoxia-induced PASMCs proliferation still uncertain. Previous research results suggest that the expression of lncRNA- metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was changed after hypoxia exposure. MALAT1 regulates the proteins expression which contributes to the proliferation of PASMCs. We hypothesis that MALAT1 was mediated the molecular and signaling transduction systems which involved in hypoxia-induced PASMCs proliferation. Following study was designed to confirm our hypothesis. First, investigate the expression and distribution pattern of MALAT1 in pulmonary hypertension patients and hypoxia exposure mouse models. Second, investigate the role of MALAT1 in PASMCs proliferation and the exactly pathway. Third, identify the exactly molecular mechanism, such as the target microRNAs; target proteins and the interaction network. The results of this study will reveal the new mechanism of MALAT1 in regulating PASMCs proliferation; and can provide potential therapeutic and pharmaceutical strategies for hypoxic pulmonary hypertension.

英文关键词： pulmonary arterials smooth muscle cells;hypoxic pulmonary hypertension;proliferation;long non-coding RNA;MALAT1