PVT1环状RNA在肝癌中的功能及其分子机制研究

Circular RNA (circRNA) is a type of RNA that forms a covalently closed continuous loop. Recently, circRNAs are found to be widespread and highly abundant due to the high-throughput sequencing and novel computational approaches. They have been categorized as noncoding RNA with potential as gene regulators. However, the expression, function and mechanism of circRNAs in human cancer remain largely unknown. In this study, we had identified a set of circRNAs differently expressed in hepatocellular carcinoma (HCC) by using high-throughput RNA sequencing. One of these circRNAs,derived from exon3 of PVT1, was found to be significantly upregulated in HCC. Furthermore, functional assay by RNA interference indicated that circ-PVT1 could promote HCC cell proliferation，migration and invasion. In this project, we will focus on the correlation between the circ-PVT1 expression and clinicopathological features of tumor as well as the function and molecular mechanism of circ-PVT1 in HCC. This will provide new insights into the diagnosis and treatment of HCC .

环状RNA(Circular RNA)是一类非线性RNA分子，是最近非编码RNA研究领域的热点。近年来随着RNA测序（RNA sequencing, RNA-seq）和生物信息学技术的发展，大量的环状RNA被发现，但是环状RNA在肿瘤中的表达情况，临床意义，功能和作用的分子机制还不清楚。本研究前期通过高通量RNA测序分析并鉴定了一批肝癌相关的环状RNA，其中有一个明显上调的环状RNA引起我们关注，它是由PVT1基因的第三个外显子环化形成的（命名为circ-PVT1)。我们进一步在大样本量的组织中验证也发现circ-PVT1在肝癌中显著上调，而且实验发现circ-PVT1能促进肝癌细胞的增殖及迁移侵袭。本课题将在前期工作的基础上进一步分析circ-PVT1的表达与临床病理特点的相关性，circ-PVT1在肝癌发生发展中的功能及其作用的分子机制，为肝癌的诊断治疗提供新的思路及候选靶点。

环状RNA (Circular RNA)是一类闭合的环形RNA分子。近年来随着RNA测序（RNA sequencing, RNA-seq）和生物信息学技术的发展，大量的环状RNA被发现，但是环状RNA在肿瘤中的表达情况，临床意义，功能和作用的分子机制还不清楚。本研究通过高通量RNA测序分析鉴定了一批肝癌和胃癌相关的环状RNA，其中有一个明显上调的环状RNA引起我们关注，它是由PVT1基因的第三个外显子环化形成的（命名为circPVT1)。另外，在胃癌组织中circPVT1所在基因区域的基因拷贝数是扩增的，并且与circPVT1的表达量正相关，提示circPVT1在癌中高表达可能由于拷贝数扩增。circPVT1在胃癌细胞中是稳定存在的，并且主要位于细胞浆。下调circPVT1的表达后，胃癌细胞的增殖能力受到抑制。circPVT1可以作为miR-125家族的“分子海绵”发挥作用。circPVT1是胃癌病人独立的预后因子。