新型分子标志物snoRNA在非小细胞肺癌中的研究与应用

项目名称： 新型分子标志物snoRNA在非小细胞肺癌中的研究与应用

项目编号： No.81502587

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 高卓

作者单位： 哈尔滨医科大学

项目金额： 18万元

中文摘要： 核仁小RNA（snoRNAs）是一类非编码RNA，在脊椎动物中由基因的内含子加工生成，与宿主基因的表达在同一转录过程中完成。基于二者共表达这一特殊模式，我们提出以癌基因内含子加工生成的snoRNAs作为分子标志物，通过检测血清中snoRNAs的含量反映肿瘤中的宿主癌基因的表达水平，进而得到分子标志物的新的筛选方法。前期通过NGS平台及大样本量检测筛选到数十个在非小细胞肺癌（NSCLC）中特异性高表达的snoRNAs。我们将以SNORA30 和 SNORD10为例（宿主基因为癌基因SRCAP和EIF4A1），确认snoRNAs与宿主基因在NSCLC组织样本中的表达相关性，探究二者表达间相互调控的可能性。其次，分析血清样品中snoRNAs与肿瘤中宿主癌基因表达的相关性。从而为NSCLC的诊断提供新的分子标志物，并为肿瘤及其他疾病分子标志物的筛选提供新的模式。

中文关键词： 非小细胞肺癌；核仁小RNA；宿主基因；分子标志物

英文摘要： Emerging evidence indicates that small nucleolar RNAs (snoRNAs), a class of small non-coding RNAs, may play important function in tumorigenesis. A large proportion of genes hosting snoRNAs in their introns, and the expression were in the same transcriptional process with snoRNAs. Non-small cell lung cancer (NSCLC) is the most common cancer killer for people. Systematically characterizing snoRNAs in NSCLC will develop biomarkers for its detection and prognostication. Since snoRNAs have a very special co-expression pattern with the host genes, we hypothesize that snoRNAs processed from oncogenes will be highly transcribed and show high levels of production, and could be an effective biomarker for rapid diagnosis. We hope the amount of snoRNAs in serum could reflect the expression levels of oncogenes in tumor. In our previous study, we found dozens of snoRNAs had higher expression levels in NSCLC by next generation sequencing and tissue sample verifications. SNORA30 and SNORD10 were selected for further study, whose host genes are SRCAP and EIF4A1, repectively. The results showed there is a correlation between the snoRNAs and host gene expression levels in lung cancer cell lines. We will further verify the correlation between snoRNAs and host genes expression levels in NSCLC tissue samples, also expression correlation between snoRNAs (SNORA30 and SNORD10) in serum and their host genes in tumor; in addition, the availablity of regulation mechanism between them will also be explored. Our research will provide potential biomarkers for the detection and prognostication of NSCLC，also a new screening method of biomarkers for tumor and other diseases.

英文关键词： Non-small cell lung cancer ;snoRNAs;Host-gene;Biomarker