长链非编码RNA AC074286.1在食管鳞癌中的生物学功能及其表观遗传机制

项目名称： 长链非编码RNA AC074286.1在食管鳞癌中的生物学功能及其表观遗传机制

项目编号： No.81472335

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郭炜

作者单位： 河北医科大学

项目金额： 80万元

中文摘要： 表观遗传学机制在肿瘤中的作用越来越受到重视。申请者在前期的研究中发现，启动子区CpG岛高甲基化可能是导致重要的抑癌基因RASSF1A和RKIP在食管鳞癌中表达降低的重要机制之一。随着研究的深入，我们发现在食管鳞癌中显著低表达的一个lncRNA AC074286.1与RASSF1A和RKIP同为miR-181a/b/c/d及miR-4262的靶基因，且甲基化等表观遗传学改变有可能是导致其在食管鳞癌中表达降低的机制之一。本研究通过检测AC074286.1在食管鳞癌中的生物学作用，分析其作为ceRNA是否通过与miRNA竞争性结合从而调控RASSF1A及RKIP的表达，并对导致其在食管鳞癌中表达降低的表观遗传学机制进行探讨，为明确AC074286.1在食管鳞癌发生发展中的作用及可能的分子机制提供有力的实验数据，为食管鳞癌的发生发展提供表观遗传学上的证据，并为食管鳞癌的治疗和预后判断提供分子靶点。

中文关键词： C06_食管肿瘤；长链非编码RNA；AC074286.1；ceRNA；表观遗传学机制

英文摘要： Recently the effect of epigenetic mechanisms in tumor etiology was regarded increasingly. We have found that aberrant promoter CpG island methylation may be one of the mechanisms that lead to loss or down expression of important tumor suppressor genes-RASSF1A and RKIP in esophageal squamous cell carcinoma (ESCC). With the in-depth study, we found that both a lncRNA AC074286.1 (which showed significantly decreased expression in esophageal squamous cell carcinoma) and RASSF1A and RKIP were target genes of miR-181a/b/c/d and miR-4262. Epigenetic alterations such as methylation may be one of the mechanisms which lead to the decreased expression of AC074286.1 in ESCC. The present study was to detect the biological function of AC074286.1 in ESCC, investigate the effect of AC074286.1 as ceRNA on the expression of RASSF1A and RKIP, and analyze the epigenetic mechanisms which lead to the decreased expression of the gene in ESCC, in order to offer experimental data of AC074286.1 on the occurrence and development of ESCC, provide epigenetic evidence for the mechanisms of ESCC etiology, and provide molecular target for ESCC treatment and prognosis.

英文关键词： esophageal squamous cell carcinoma;long non coding RNA;AC074286.1;ceRNA;epigenetic mechanism