长链非编码RNA HOXD-AS1促进人肝细胞癌增殖的作用及分子机制研究

项目名称： 长链非编码RNA HOXD-AS1促进人肝细胞癌增殖的作用及分子机制研究

项目编号： No.81502136

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 孙晋

作者单位： 西安交通大学

项目金额： 18万元

中文摘要： 长链非编码RNA（lncRNA）作为新型调控分子可参与肝细胞癌（HCC）的发生发展。我们前期研究发现lncRNA HOXD-AS1在HCC细胞中高表达，其沉默后细胞增殖减缓且周期阻滞在G2/M期，提示HOXD-AS1可能参与调控HCC的增殖。本项目拟在前期基础上，通过观察HCC细胞过表达和沉默HOXD-AS1后细胞增殖、周期、裸鼠成瘤的变化情况并分析临床样本HOXD-AS1表达与HCC病理特征的相关性，从细胞、动物、临床水平明确HOXD-AS1在HCC细胞增殖中的作用；采用RNA pull-down、RNA免疫共沉淀、基因芯片、ChIP-qPCR等技术解析HOXD-AS1通过结合蛋白调控下游靶基因的作用机制及其调控的信号通路，进而阐明HOXD-AS1促进HCC增殖的分子机制，为从lncRNA角度揭示HCC发生发展的分子机制提供新线索，同时为HOXD-AS1应用于临床诊断治疗提供理论依据。

中文关键词： 肝和肝内胆管肿瘤；长链非编码RNA；HOXD-AS1；增殖

英文摘要： It has been demonstrated that long noncoding RNA (lncRNA) play important roles in the occurrence and progression of hepatocellular carcinoma (HCC). Our previous study found HOXD-AS1, a lncRNA from HOXD loci, was highly expressed in hepatoma cells and its knockdown could inhibit the proliferation of HCC cells in vitro and cell cycle arrest at G2/M phase, implying that HOXD-AS1 may take part in proliferation of HCC. Based on our previous study, this project aims to clarify the role of HOXD-AS1 in HCC proliferation at the cellular, animal and clinical level by investigating the proliferation, cell cycle and tumor formation in nude mice of HCC cells that overexpress and knockdown HOXD-AS1 and examining the of HOXD-AS1 expression in HCC clinical samples and its relationship with clinicopathological characteristics, and to illustrate the molecular mechanism of promoting proliferation of hepatocellular carcinoma of HOXD-AS1 by identifying its binding protein and target genes and analyzing the mechanism of HOXD-AS1 regulating target genes through binding and related signaling pathway using RNA pull-down, RNA immunoprecipitation, microarray and ChIP-qPCR, etc. This project will provide new clues to revealing the molecular mechanism of pathogenesis and progression of HCC from the perspective of lncRNA, and will also offer the theoretical basis for clinical translational research of HOXD-AS1.

英文关键词： Hepatocellular carcinoma ;Long noncoding RNA;HOXD-AS1;Proliferation