长链非编码RNA Bc008363调控α-激酶Alpk-1促进胰腺癌细胞上皮-间充质转化诱导侵袭转移

项目名称： 长链非编码RNA Bc008363调控α-激酶Alpk-1促进胰腺癌细胞上皮-间充质转化诱导侵袭转移

项目编号： No.81502489

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： 李峤

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 胰腺癌侵袭性强，术后复发转移率高，预后差，因此对于研究胰腺癌侵袭转移的上皮-间充质转化（EMT）发生机制及治疗靶点已成为近年的研究热点；同时国内外对于长链非编码RNA在肿瘤中的作用逐渐受到关注，其与乳腺癌、肝癌等多种肿瘤发生有关，但在胰腺癌发生发展中的作用仅仅处于起步阶段，对于其是否参与EMT进程仍未明确。我们的前期研究发现lncRNA- Bc008363 在胰腺导管腺癌组织中高表达；敲低 Bc008363 可下调Alpk-1的表达，敲低Bc008363或Alpk-1均可抑制胰腺癌细胞的侵袭。本研究拟探讨Bc008363是否通过调控Alpk-1的表达来促进胰腺癌EMT的机制；分析Bc008363 作为临床治疗预后标志物和治疗靶点的意义。从细胞实验、临床标本和动物实验等方面探讨Bc008363 与Alpk-1 的相互作用促进胰腺导管腺癌发生发展的作用及其机制。

中文关键词： C11_胰肿瘤；长链非编码RNA；预后；上皮间质化；侵袭

英文摘要： Pancreatic cancer is a common cancer with strong invasiveness , high rate of tumor metastasis、relapse afte postoperative and poor prognosis . So the research of epithelial - mesenchymal transition (EMT) in pancreatic cancer induced invasion and metastasis mechanism and therapeutic targets have become a hotspot in recent years;LncRNAs have been reported being involved with the development of several cancers, such as breast cancer and hepatocellular carcinoma. However, there are few studies of pancreatic cancer related lncRNAs, it is still not clear whether to participate in the EMT process. In our previous research, we found that lncRNA - Bc008363 was overexpressed in human pancreatic ductal adenocarcinoma cancer. Downregulation of Bc008363 significantly decreased the expression of Alpk – 1. Downregulation of Bc008363 or Alpk – 1 can inhibit pancreatic cancer cell invasion and metastasis. Based on our preliminary datas we will reveal the mechanism of Bc008363 promoting the EMT process in pancreatic cancer by regulating Alpk – 1 ; discuss the significance of Bc008363 in clinical prognostic marker and therapeutic target. In a word, we will explore the mechanism by which Bc008363 interacts with Alpk – 1 and promotes the development of pancreatic cancer via in vitro, in vivo experiments and patient samples.

英文关键词： C11_pancreatic cancer;long non-coding RNA;prognosis;epithelial- mesenchymal transition ;invasion