LncRNA NEAT1在结直肠癌早期诊断与预后预测中的作用及其调控结直肠癌发生发展的分子机制研究

项目名称： LncRNA NEAT1在结直肠癌早期诊断与预后预测中的作用及其调控结直肠癌发生发展的分子机制研究

项目编号： No.81472620

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： 徐烨

作者单位： 复旦大学

项目金额： 72万元

中文摘要： 长链非编码RNA（lncRNAs）在肿瘤发生发展及转移过程中具重要作用，但绝大部分lncRNAs的功能尚不清楚。本课题组前期基于外周血基因组表达谱的研究发现lncRNA NEAT1高表达与结直肠癌发生密切相关，生物信息学检索及数据再分析提示NEAT1与组蛋白甲基化调控酶SUV39H1呈负相关。进一步研究发现NEAT1_v2在肠癌组织低表达与肿瘤转移、生存时间缩短显著相关。本课题首次系统地研究NEAT1在肠癌外周血、癌/癌旁组织的差异表达模式、预后价值及其分子机制，尤其是NEAT1与组蛋白甲基化调控酶SUV39H1的关系和相关机制，期望全面阐述NEAT1在肠癌发生发展中的作用，构建肠癌早期诊断模型和分子预测模型，为肠癌的个体化治疗提供参考。

中文关键词： C08_结；直肠肿瘤；长链非编码RNA；核富集常染色体转录产物1；表观遗传学；转录本

英文摘要： Long non-coding RNA (lncRNA) plays crucial role in carcinogenesis, progress and metastasis of solid tumors. However, the function of most lncRNA is not clear. Our preliminary study using gene expression microarray revealed elevated NEAT1 expression in peripheral blood of colorectal carcinoma (CRC) patients compared with healthy participants. Bioinformatics search and data re-analysis indicated significant negative correlation of NEAT1 expression with histone methyltransferase SUV39H1. RT-PCR results demonstrated decreased NEAT1 expression in CRC tumor and peritumor tissues compared with peripheral blood. Decreased intratumoral NEAT1 expression significantly correlated with presence of distant metastasis and reduced over-all survival. For the first time, at least to our knowledge, we systematically studied differential expression pattern and prognostic impact of NEAT1 in peripheral blood, intratumoral and peritumoral tissues of CRC patients. The molecular mechanism, focusing on histone methylation mediated by SUV39H1, was further elucidated by in vitro and in vivo models. We aim to apply NEAT1 as new diagnostic and prognostic biomarker, which would guide individualized therapy for CRC patients.

英文关键词： Colorectal cancer;lncRNA;nuclear-enriched autosomal transcript1(NEAT1);epigenetics;transcription