乙肝病毒X蛋白激活调控LncRNA在介导慢性肝炎恶性转化中的作用研究

慢性乙型肝炎病毒(HBV) 关键基因HBx密切相关于慢性非可控性肝炎向原发性肝癌恶性转化过程。长链非编码RNAs（lncRNAs）是一类具有生物功能保守分子，在肿瘤中具有组织特异性表达。本研究组应用Human LncRNA Microarray分析HBx诱导肝细胞中lncRNA表达谱发现，所诱导表达lncRNAs参与肝癌发生过程中各种信号传导通路，提示这类分子在HBV相关肝癌发生过程中具有不可忽视的作用。本研究在原有工作基础上拟通过ChIRP、RIP，ChIP-on-Chip等高通量方法，以HBx为关键分子深入研究HBV致肝癌过程中关键节点lncRNAs分子及调控网络，结合动物模型及HBV感染不同发展时期临床样本体外模型，确认HBV感染时间和感染过程中节点lncRNAs及其表观遗传调控作用，寻找节点表观遗传变化及其相互作用，为HBV慢性感染至恶性转化发生的表观遗传调控网络提出新的理论见解。

HBx is a pivotal gene of chronic hepatitis B virus, closely associating with the process from uncontrollable hepatitis to primary hepatic carcinoma. Long non-coding RNAs (lncRNAs) are conservative molecules, which express in specific tissues in tumor. Our study shows that the differential expression lncRNA induced by HBx may participate in various of signaling transduction pathway in hepatocellular carcinogenesis ananlyzed by Human LncRNA Array, implying it is necessary to study on the function and key point pathway of these lncRNA in HBV associated hepatic carcinoma. The project will employ ChIRP, RIP, ChIP-on-Chip to lucubrate the regulation network comprising HBx-lncRNA- hepatic carcinoma based on the previous work. Meanwhile, identify epigenetic regulation network of “ Key point ” lncRNA at different phases and process of HBV infection in animal model and clinical samples in form of HBx continuous and intermittent expression, aiming at providing a novel theoretical view for epigenetic process from HBV chronic infection to malignant transformation.