LncRNA-HOTAIR介导酸性微环境下胰腺癌细胞侵袭转移的机制研究

项目名称： LncRNA-HOTAIR介导酸性微环境下胰腺癌细胞侵袭转移的机制研究

项目编号： No.81502076

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： 邓世昌

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 胰腺癌细胞发生侵袭转移是导致死亡的主要原因。胰腺癌酸性微环境与侵袭转移密切相关，其机制尚未明确。课题组研究发现胰腺癌细胞在酸性条件下发生上皮间质转化（EMT）且侵袭能力增强，同时长链非编码RNA-HOTAIR（lncRNA-HOTAIR）表达上调。文献证实lncRNAs在肿瘤侵袭转移中发挥重要作用。前期研究证实HOTAIR在胰腺癌组织中高表达并能调控胰腺癌细胞EMT。由此推测， HOTAIR可能介导酸性微环境下胰腺癌细胞的EMT，从而促进侵袭转移。本研究拟检测胰腺癌组织及不同酸度培养下胰腺癌细胞HOTAIR-EMT信号通路的表达；调控体内及体外胰腺癌细胞微环境酸度及上述信号通路，观察胰腺癌细胞侵袭转移能力的变化。本研究以胰腺癌酸性微环境与胰腺癌细胞之间的相互作用为切入点，深入探讨了酸性微环境下lncRNAs调控胰腺癌细胞发生侵袭转移的分子机制，为胰腺癌的防治提供新靶点和新策略。

中文关键词： 胰腺外分泌肿瘤；酸性微环境；长链非编码RNA-HOTAIR；侵袭转移；上皮间质转化

英文摘要： Pancreatic cancer(PC) is the most aggressive solid tumor with <5% survival after 5 years. Recent studies suggest that interaction between tumor and its microenvironment act as a dynamic process promoting tumor growth, metastasis and invasion, but the mechanism has not been identified. Pancreatic cancer is characterized by an acidic microenvironment. Our previous results showed that acidic microenvironment enhanced metastasis and invasion of pancreatic cancer cells, while the lncRNA-HOTAIR (long non-coding RNA HOTAIR) was up-regulated. Given that previous reports demonstrated HOTAIR expression in patients has been correlated with enhanced cancer metastasis and has linked to invasiveness and EMT of cancer cells, as well as evidence from our lab demonstrated HOTAIR was over-expressed in pancreatic cancer and related to more aggressive tumor stage, we hypothesize that HOTAIR may be up-regulated in acidic stress and then facilitated the EMT process of pancreatic cancer, leading progression of pancreatic cancer. In this study, we detect the gradient of pH value in pancreatic cancer and normal pancreas and explore the expression of HOTAIR-EMT pathway according to the pH value. Further, microenvironment pH value and HOTAIR-EMT pathway will be regulated to observe the metastasis and invasion of pancreatic cancer cells in vitro or in vivo. Starting from the regulatory role of the tumor microenvironment on metastasis and invasion of pancreatic cancer, our present research will, from the perspective of lncRNAs adaptive response to tumor microenvironment stress, focus on the signal transmission among the acidic microenvironment, lncRNAs and pancreatic cancer cells and explore the molecular mechanism by which acidic microenvironment promotes metastasis and invasion of pancreatic cancer. It will provide novel targets and strategies for research on prevention and treatment of pancreatic cancer.

英文关键词： pancreatic cancer;acidic microenvironment;lncRNA-HOTAIR;metastasis and invasion ;EMT