长链非编码RNA HULC在肝癌中的生物学功能及机制研究

项目名称： 长链非编码RNA HULC在肝癌中的生物学功能及机制研究

项目编号： No.81201567

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： 李丹

作者单位： 中国医学科学院肿瘤医院

项目金额： 23万元

中文摘要： 长链非编码RNA是一类由基因组转录但并不翻译的长度大于200bp的RNA分子，它们通过不同机制，如RNA-RNA碱基配对，RNA蛋白相互作用，RNA-DNA相互作用等，在细胞调控的各个层面中发挥功能，如参与染色质修饰、转录调节、剪切加工、RNA稳定性调节等。HULC RNA是一种在肝癌中特异高表达的长链非编码RNA分子，长度大约在500bp，具有polyA尾的结构，但其在肝癌中高表达的生物学功能和分子机制鲜有报道。我们的前期研究发现HULC RNA能够促进细胞的增殖、迁移及侵袭能力，并能抑制自噬和顺铂诱导的细胞凋亡，且HULC RNA与YB1蛋白相互作用。因此，本项目将重点研究HULC RNA促进细胞恶性表型的原因和机制，阐明HULC RNA与YB1蛋白的结合机制及功能，促进我们对长片段非编码RNA在肿瘤病因学中功能的认知，并为未来HULC RNA作为肿瘤诊断标志物及治疗靶点提供理论支持。

中文关键词： HULC；YB-1；长链非编码RNA；磷酸化；肿瘤发生

英文摘要： Non-coding RNAs (ncRNAs), which transcript from DNA but do not encode protein, contein high density of stop codons or lack extensive "Open Reading Frame".They have been shown to be involved in different levels of cell regulations including chromalsome modification, transcription regulation, RNA splicing and RNA stability, via RNA-RNA basepair, RNA-protein interaction, RNA-DNA interaction. Recently, dysregulated expressions of ncRNAs have been reported in many types of cancers, indicating that they maybe play critical roles in tumorigenesis. HULC (Highly Up-reglated in Liver Cancer), is a ncRNA characterized in hepatocelluar carcinoma (HCC). The HULC gene locates at 6p24.3 and the transcripts of this gene is spliced and polyadenylated like mRNA to form a 500bp RNA. Feature of the HULC RNA sequence is the high density of stop codons in the small potential reading frames and can not encode a protein product. HULC RNA can be detected in HCC tissues as well as in the blood of HCC patiens at a high level. It has also been reported that HULC expression is not confined to HCC, but also to those colorectal carcinomas that metastasize to the liver. HULC RNA can therefore be used as specific molecular markers for HCC. However, little is known about the function of HULC RNA and its molecular mechanism. In the previous study

英文关键词： HULC；YB-1；LncRNA；phosphorylation；tumorigenesis