结直肠癌发生相关lncRNAs的筛选、验证及其血清学诊断价值研究

项目名称： 结直肠癌发生相关lncRNAs的筛选、验证及其血清学诊断价值研究

项目编号： No.81472025

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王传新

作者单位： 山东大学

项目金额： 80万元

中文摘要： 长链非编码RNAs（lncRNAs）是新发现的具有基因表达调控作用的一类分子，其异常表达可导致肿瘤的发生，而它们与结直肠癌发生的关系以及是否可作为分子标志物用于肿瘤诊断迄今尚未阐明。本课题组前期利用高通量lncRNAs芯片初筛了39个结直肠癌、结直肠腺瘤及癌旁正常组织差异表达lncRNAs。为此，本研究拟扩大临床样本进行验证，建立结直肠癌发生相关lncRNAs差异表达谱；然后通过体外细胞实验、体内裸鼠模型及lncRNA-mRNA共表达分析，探讨差异lncRNAs在结直肠癌发生中的作用；最后以血清exosomes为检测载体，运用RT-qPCR技术对结直肠癌、结直肠腺瘤以及健康对照者血清进行大样本、多层次验证，评价血清exosomes中差异lncRNAs对结直肠癌的临床诊断价值及转化医学意义。本研究不仅有助于进一步明确lncRNAs在结直肠癌发生中的作用，也将为结直肠癌的实验室诊断提供依据。

中文关键词： 结直肠癌；肿瘤标志物；长链非编码RNA；分子诊断

英文摘要： Long noncoding RNAs (lncRNAs), a novel class of noncoding RNAs, were recently found to be dysregulated in various diseases and have critical regulatory roles in wide array of cellular functions. The altered expression of lncRNAs can result in aberrant gene expression products which may contribute to cancer biology. However, the overall pathophysiological contributions of lncRNAs to tumorigenesis of colorectal cancer (CRC) have not been fully elucidated and it is also of paramount important to develop novel molecular markers for CRC diagnosis based on differentiate lncRNAs profiles, which could help patients prevent delay of effective treatment. To define associations between lncRNAs and CRC, we sough to identify the specific lncRNAs expression profiles based on the thesis of normal mucosa-adenoma-carcinoma to evaluate the function and diagnostic value. In our previous studies, high-throughput lncRNAs chip analysis was performed in tissue samples of CRC patients, adenoma patients and healthy controls. Thirty-nine lncRNAs were found differently expressed. In further studies, we will verify the 39-lncRNAs profile in a large cohort and establish the specific lncRNAs expression profile. The vitro assays including cell proliferation, colony formation, cell apoptosis, cell cycle and the vivo nude mice experiments combined with lncRNA-mRNA coexpression analysis will be used to demonstrate the role of lncRNAs in the tumorigenesis of CRC. In addition, based on the important advances with the introduction of exosomes, we will further assess the diagnostic values of differential lncRNAs by RT-qPCR in serum exosomes, which may show us medically values on early detection of CRC.

英文关键词： colorectal cancer;tumor marker;long non-coding RNA;molecular diagnosis