RERT-lncRNA调控EGLN2在肝细胞肝癌发生中的作用机制研究

项目名称： RERT-lncRNA调控EGLN2在肝细胞肝癌发生中的作用机制研究

项目编号： No.81201574

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 何艳

作者单位： 苏州大学

项目金额： 23万元

中文摘要： 长链非编码RNAs（lncRNAs）在基因组中广泛表达并以RNA的形式在多种层面调控基因表达。已有研究表明lncRNAs的异常表达与肿瘤的发生发展密切相关。我们近期的研究发现：位于prolyl羟化酶（EGLN2）远端启动子的一个遗传多态(rs10680577)与肝细胞肝癌（HCC）的发生、预后及EGLN2表达存在显著性相关，而这种相关不是该多态影响EGLN2启动子的转录而调控其表达。我们注意到EGLN2及其上游基因间存在一个通读长链非编码RNA（RERT-lncRNA），我们推测该多态可能通过影响长链非编码RNA的表达从而实现对其下游基因EGLN2的调控，进而参与HCC的发生和预后。本课题拟采用基因型-表型关联结合功能实验方法研究遗传多态、RERT-lncRNA和EGLN2三者间的依存关系及其对肿瘤细胞特征的影响，以期阐明遗传因素-lncRNA-EGLN2通路在HCC发生发展中的作用机制。

中文关键词： 长链非编码RNA；遗传多态；肝细胞肝癌；prolyl 羟化酶；生物信息学

英文摘要： As a new class of transcripts, long non-coding RNAs (lncRNAs) have been recently found to be pervasively transcribed in the genome. Multiple lines of evidence increasingly link dysregulations of lncRNAs to multiple human cancers. However, the biological functions of the vast majority remain unknown. Recent progress suggests that the involvement of lncRNAs in cancer could be far more prevalent than previously appreciated. Our previous studies have identified a novel polymorphism (rs10680577) within distal promoter of hypoxia-inducible factor prolyl hydroxylase 1 (PHD1, also known as EGLN2) which was significantly associated with both HCC incidence and prognosis in a Chinese population. Functional experiments revealed a strong genotype-phenotype correlation between rs10680577 and EGLN2. However, results from luciferase-based transient transfection system indicated that this correlation was not mediated by a differential promoter polymorphism-associated regulatory mechanism. On the other hand, we noticed that there existed a 2849-bp RAB4B-EGLN2 read-through long non-coding RNA (RERT-lncRNA) overlapping EGLN2 and the upstream RAB4B. Considering the fact that rs10680577 was located within RERT-lncRNA, we assume that rs10680577 may influence RERT-lncRNA expression by interrupting its folding structures, which in turn

英文关键词： IncRNA；gentic polymorphism；hepatocelluar caricinima；EGLN2；bioinformatics