ERBB4 3'非翻译区致病变异的发现及其在慢性HBV感染和肝细胞癌中的作用

项目名称： ERBB4 3'非翻译区致病变异的发现及其在慢性HBV感染和肝细胞癌中的作用

项目编号： No.31471189

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 刘瑶

作者单位： 苏州大学

项目金额： 85万元

中文摘要： ERBB4是EGFR家族成员之一，与该家族其他成员相比，ERBB4研究比较薄弱。我们前期发现，一些应激或损伤因子可诱导ERBB4表达；大规模人群实验、临床组织标本和动物研究发现，ERBB4可能是慢性HBV感染和肝细胞癌的保护分子。我们进一步发现，ERBB4 3'非翻译区(UTR)rs6147150的12碱基的插入/缺失变异可影响miRNA结合，从而调控ERBB4的表达。携带12碱基插入的个体ERBB4表达量更低，更容易发生慢性HBV感染。值得注意的是，ERBB4的3'UTR近8000碱基长，然而根据目前的数据库，并不能发现3'UTR的其它多碱基变异或罕见变异，因此有必要对ERBB4 3'UTR重测序，寻找致病变异，并进一步阐明致病变异对ERBB4的调控机制及其意义。本研究将对ERBB4 3'UTR的调控机制进行系统探索，并将深入探讨ERBB4在慢性HBV感染和肝细胞癌中的作用。

中文关键词： 乙型肝炎病毒；肝细胞癌；ERBB4；3'非翻译区

英文摘要： ERBB4 is a member of EGFR family, which has been studied less compared with its family members. Previously, we have found that stress or some injury factors may up-regulate ERBB4 expression and that ERBB4 may be protective factors from both chronic HBV infection and HCC identified from population study, clinical tissue samples and animal models. We further identified rs6147150, a 12 base pairs (bp) insertion/deletion (Ins/Del) in the 3' untranslated region (UTR) of ERBB4, may affect miRNA binding and regulate the expression of ERBB4. Individuals carrying 12 bp insertion exhibited lower ERBB4 expression and were prone to chronic HBV infection. It is worth noting that the 3'UTR of ERBB4 was nearly 8000 bp long, however, it is unable to identify other poly-bp variations or rare variations in the 3'UTR of ERBB4 based on current databases. Thus it is necessary to re-sequence the 3'UTR of ERBB4 to identify casual variations and elucidate their regulatory roles in ERBB4. In summary, we will explore the regulatory mechanism of the 3'UTR of ERBB4 thoroughly and elucidate the role of ERBB4 in chronic HBV infection and HCC in this study.

英文关键词： hepatitis B virus;hepatocellular carcinoma;ERBB4;3' untranslated region