长链非编码RNA HOTAIRM1在结直肠癌中的功能研究

项目名称： 长链非编码RNA HOTAIRM1在结直肠癌中的功能研究

项目编号： No.81201557

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： 张红河

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 长链非编码RNA不仅参与了细胞周期、分化、凋亡和衰老，以及细胞间或细胞内核浆运输等细胞学过程，而且还具有表观遗传学调控、转录调节、转录后及翻译调节染色质重塑等重要的分子生物功能。HOTAIRM1是最近新发现的一条长链非编码RNA，本课题组先期实验结果表明HOTAIRM1在结直肠癌中表达明显降低，并且将HOTAIRM1干扰后细胞增殖增加，但其在肿瘤中的生物学机制仍不明确，因此本研究以结直肠癌为疾病模型，以HOTAIRM1为靶点，拟采用表达载体或RNA干扰技术确定其在结直肠癌细胞中的生物学功能；利用MSP和BSP等技术研究HOTAIRM1自身表达是否受甲基化调控及特异性甲基化位点；订制HOX基因簇的低密度芯片，筛选HOXAIRM1下游相关的HOX基因簇成员，采用功能缺失或增补实验进一步明确HOTAIRM1通过HOX基因簇发挥生物学功能；本项目的完成将为结直肠癌的发生发展阐释全新机制。

中文关键词： 长链非编码RNA；结直肠癌；HOTAIRM1；功能；

英文摘要： Long noncoding RNAs (lncRNAs) play intrinsic roles as RNA, which may participate in various biological processes through distinct mechanisms. For example, lncRNAs have been implicated in cell cycle control, cell differentiation and apoptosis, while others are involved in epigenetic silencing, transcriptional and translational control, and splicing regulation. Therefore, there is a powerful suggestive link between lncRNAs and disease. But the role of lncRNA in malignant tumor remains unknown. HOTAIRM1 is a novel lncRNA, which was identified recently.We found its expression in colorectal cancer was significantly down regulated. Furthermore, we want to eluciate the biological function of HOTAIRM1 in colorectal cancer by ectopic expression or knockdown of HOTAIRM1. And whether the HOXAIRM1 expression is regulated by aberrant DNA methylation will be studied by MSP and BSP. Otherwise we also want to describe that HOX cluster is the down stream target of HOTAIRM1. Taken together, completion of the study will clarify a new regulation pathway and carcinogenesis mechnism in colorectal cancer and may highlight promising targets of diagnostic and therapeutic value for colorectal cancer in the future.

英文关键词： LncRNA；Colorectal cancer；HOTAIRM1；Role；