低氧微环境下长链非编码 RNA RP11-70F11.8 促进肝癌侵袭转移的分子机制

项目名称： 低氧微环境下长链非编码 RNA RP11-70F11.8 促进肝癌侵袭转移的分子机制

项目编号： No.81502100

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： 吕秀芳

作者单位： 南通大学

项目金额： 18万元

中文摘要： 低氧微环境与肿瘤转移高度相关，以往研究多关注与低氧相关的蛋白编码基因，对非编码RNA、特别是长链非编码RNAs（lncRNAs）认识不足。lncRNAs在肝细胞癌的发生发展过程中具有重要作用，其数量、功能及作用机理繁复，仍有大量的与肝细胞癌相关的lncRNAs有待发现和揭示。我们前期采用lncRNA表达谱芯片对低氧处理的人肝癌细胞分析，发现低氧可诱导lncRNA RP11-70F11.8表达，且与HIF-1α的表达呈正相关；干扰lncRNA RP11-70F11.8显著抑制低氧诱导的肝癌细胞侵袭和迁移，提示该lncRNA可能在低氧微环境下，通过调控肝癌转移相关mRNAs的表达继而促进肝癌侵袭转移。我们拟通过分子、细胞及动物模型等体内外实验，研究低氧微环境下该lncRNA对肝癌细胞侵袭迁移的作用机制，分析该lncRNA表达水平及肝癌患者临床病理之间的关系，探讨其在肝癌预后判断中的价值。

中文关键词： 肝和肝内胆管肿瘤；低氧微环境；长链非编码RNA；侵袭；转移

英文摘要： There is a close relationship between hypoxic microenvironment and tumor metastasis. Previous studies paid more attention to the expression and function of mRNAs associated with hypoxic microenvironment, but not the noncoding RNAs especially for long noncoding RNAs (lncRNAs). lncRNAs play important roles in multiple biological processes, including carcinogenesis, migration and invasion of hepatocellular carcinoma (HCC). There is a lot of lncRNAs in hepatocellular carcinoma to be revealed for the complexity of numbers, functions and mechanisms of lncRNA. In our preliminary study, we identified differentially expressed lncRNAs and mRNAs in SMMC-7721 cells cultured in hypoxia and normoxia by Human LncRNA Microarray analysis. We found that one of the differentially expressed lncRNAs, RP11-70F11.8, was positively related with HIF-1 alpha, and knowckdown of RP11-70F11.8 significantly inhibited invasion and migration induced by hypoxia in HCC cells. Therefore, we conclude that RP11-70F11.8 may promote the invasion and metastasis of HCC by regulating mRNAs expression in hypoxia. We attempt to perform our study for RP11-70F11.8 by molecular and cellular experiments and animal model in vivo and in vitro. We will investigate the effect and regulatory mechanism of RP11-70F11.8 on the invasion and migration of HCC cells in hypoxic microenvironment, analyze the relationship between levels of the lncRNA expression and clinical pathology of HCC patients, and explore its potential capacity in HCC prognosis.

英文关键词： hepetoma and intrahepatic cholangiocarcinomas ;hypoxic microenvironment;long non-coding RNA;invasion;metastasis