LncRNA-LINC01133作用机制以及在胆囊癌中功能研究

Long non-coding RNA (lncRNA) plays an important role in regulation of gene expression, and thus has attracted a lot of attention, especially in the field of cancer research. However, its relevant research in gallbladder cancer has just begun. In our previous work, we have identified a novel lncRNA-LINC01133, which might has a biological effect in gallbladder cancer, by lncRNA microarray. The function study has demonstrated that LINC01133 promotes proliferation and invasion of gallbladder cancer cells. In addition, the further gene microarray and bioformatic analysis has identified that LINC01133 plays its biological role via downregulating nearby genes and combining miRNA. In this study, we plan to do the structure identification, function and mechanism research on LINC01133, and demonstrate its role in gallbladder cancer progress. To explore its mechanism, we plan to conduct the research from three perspectives, which include protein, miRNA and mRNA. Hopefully, the downstream regulation network could be clarified by this study.

长链非编码RNA（lncRNA）具有调控基因表达的重要作用，在肿瘤研究中展现了极大的研究前景。胆囊癌相关研究仍未深入进行，我们在前期研究中经过lncRNA芯片筛选并锁定了一条在胆囊癌中可能具有重要生物学功能的lncRNA-LINC01133，功能学研究提示其可调控胆囊癌细胞增殖以及转移能力，进一步利用表达谱芯片、生物信息学分析以及双荧光素酶报告实验等方法，其可能通过抑制邻近基因表达以及与多个微小RNA（miRNA）相结合的方式来发挥生物学功能。在本项目中，我们将从与蛋白结合、与miRNA、以及与RNA（非miRNA）相互作用等角度研究LINC01133的作用机制，勾勒出LINC01133下游调控网络，同时我们还拟对LINC01133进行结构鉴定、生物学活性研究、以及其在基因信息传递过程中的机制研究，并判断其在胆囊癌发生发展过程的重要意义。

胆囊癌是胆道系统中最常见的恶性肿瘤，其恶性程度极高，对放化疗不敏感，术后易于复发转移。长链非编码RNA(LncRNA)是一类长度大于200nt，不具有编码蛋白能力的RNA。其在各种肿瘤组织中存在差异表达，并且在肿瘤发生发展中起到重要作用，因此lncRNA可成为潜在的诊断分子标志物和药物设计的靶点。胆囊癌中相关lncRNA研究仍未深入进行，我们通过9对胆囊癌与癌旁组织lncRNA芯片筛选胆囊癌及癌旁差异表达的lncRNA，发现、鉴定并命名了其中一条lncRNA(linc01133, 命名为lncRNA-GAGBC)。从分子、细胞和动物水平研究lncRNA-PAGBC对胆囊癌增殖及转移的影响；并通过研究与lncRNA-PAGBC结合miRNAs及其对miRNA靶基因的影响，系统解析lncRNA-PAGBC上下游的调控网络；通过RNA pull-down结合质谱技术阐明lncRNA-PAGBC相互作用的蛋白及其影响的下游通路。本项目的研究证实lncRNA-PAGBC有望作为胆囊癌诊断及预后判断的指标及潜在治疗靶点。