长链非编码RNA HNF1A-AS1在胃癌发生发展中的作用及其诊断价值分析

项目名称： 长链非编码RNA HNF1A-AS1在胃癌发生发展中的作用及其诊断价值分析

项目编号： No.81460364

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 黄海

作者单位： 贵州医科大学

项目金额： 47万元

中文摘要： 胃癌发病率一直高居我国各种恶性肿瘤前列，五年生存率低，死亡率居第二。目前已知长链非编码RNA(lncRNA)与恶性肿瘤发生发展密切相关，是一类潜在的肿瘤分子标志物。我们前期的实验发现lncRNA HNF1A-AS1在胃癌组织中的表达较正常组织明显上调，并可在血浆中检测到，在胃癌细胞中敲降HNF1A-AS1表达可减弱细胞的增殖和迁移。经生物信息学分析，提示HNF1A-AS1可能通过表观遗传修饰调节核小体和染色质的组装，从而促进胃癌的发生和发展。为验证这一假说，本项目将采用RNA干扰、导入过表达载体、RIP、RNA pull-down等技术，从分子水平、细胞实验和动物实验等方面探讨HNF1A-AS1是否参与染色质组装及其作用机制；并比较正常人、胃炎、胃癌前病变和胃癌患者组织中HNF1A-AS1的表达水平，探讨作为生物标志物的可行性，为其在胃癌诊断和治疗监测的潜在临床应用提供理论依据和实验基础。

中文关键词： 胃癌；长链非编码RNA；标志物；机制

英文摘要： Gastric cancer is one of the most common carcinomas in China. The five-year survival rate is low, which makes gastric cancer the second leading cause of death of all cancers. Currently, long non-coding RNA (lncRNA) has been known to be associated with the development and progression of carcinomas. It is also regarded as a potential tumor biomarker. Our preliminary results showed that lncRNA HNF1A-AS1 was markedly up-regulated in the tissues of human primary gastric cancer patients compared to normal gastric tissue, and it could also be detected in the patient's plasma. Knockdown of HNF1A-AS1 expression decreased the proliferation and migration of gastric cancer cells in vitro. Bioinformatics analysis suggested that HNF1A-AS1 may promote the formation and progress of gastric cancer through epigenetically modulating the chromosome and chromatin. As proposed in this project, we will test this hypothesis by utilizing technologies including RNA interfering, adenovirus mediated over-expression, RIP and RNA pull-down to explore the role of HNF1A-AS1 in the assembly and modulation of chromatin and histone at the molecular, cellular and system levels. The expressions of HNF1A-AS1 in different tissues and plasma samples will be further compared between normal control, gastritis, precancerous lesion and gastric carcinoma. These studies will help establish the potential candidacy of HNF1A-AS1 as a biomarker for gastric carcinoma, facilitating the diagnosis and treatment monitoring of this devastating disease in the clinic.

英文关键词： Gastric cancer;lncRNA;Biomarker;Mechanism