肝细胞癌相关长链非编码RNA的发现及其功能和分子机制研究

项目名称： 肝细胞癌相关长链非编码RNA的发现及其功能和分子机制研究

项目编号： No.91440206

项目类型： 重大研究计划

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 周钢桥

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 280万元

中文摘要： 长链非编码RNA（lncRNA）在转录、转录后，以及表观遗传水平等多个层面调控基因的表达，具有多样化的生物学功能和作用机制，与肿瘤的发生发展密切相关。为鉴定与肝癌发生发展相关的lncRNAs，我们前期通过“整合组学”方法分析了40例肝癌患者的癌和配对癌旁组织的mRNA和lncRNA表达谱，发现了多个全新的肝癌相关的lncRNAs。其中lncRNA ASLNC18598可抑制肝癌细胞的增殖，并可能通过P53通路发挥作用；另一lncRNA ASLNC18342可促进肿瘤细胞的迁移，并可能通过影响组蛋白的甲基化修饰实现对靶基因的表观遗传调控。本项目拟在上述前期工作基础上，进一步系统研究这两个新型肝癌相关lncRNA的肿瘤生物学行为，确证其癌基因或抑癌基因作用；揭示其作用机制及其分子调控网络；揭示其在肝癌中异常表达的机制，及其与肝癌发生、分型、复发和转移等的临床相关性，为未来的应用研究奠定基础。

中文关键词： 功能验证；调控作用；肝细胞癌

英文摘要： Long non-coding RNA (lncRNA) regulates gene expression in multiple levels, including transcriptional, post-transcriptional and epigenetic modification. LncRNA presents various biological functions and complicated mechanisms, and is found involved in the development of multiple diseases, such as hepatocellular carcinoma (HCC). To identify HCC- related lncRNAs, the mRNA and lncRNA expression profiles of paired tumoral and peritumoral tissues from 40 HCC patients were obtained. By “integrative omics” strategy, several novel HCC- related lncRNAs were identified. Among them, the ASLNC18598 was shown to suppress the HCC cells proliferation through P53 signal pathway. Meanwhile, the ASLNC18342 was shown to promote the migration of HCC cells. Further, by cluster analysis of gene expression profile, the ASLNC18342 was shown to regulate the histone methylation of migration-associated genes. In this project, we will focus on following objects: 1) Clarifying the roles of ASLNC18598 and ASLNC18342 in the development of HCC; 2) Clarifying the underlying mechanisms and molecular network of ASLNC18598 and ASLNC18342; 3) Analyzing the relationship between the abnormal expression of these two lncRNAs and tumor processes such as tumorigenesis, progression, metastasis and recurrence.

英文关键词： Verification of function;Regulation network;Hepatocellular carcinoma