miR-92b、miR-181和miR-375调控网络靶向NLK在非小细胞肺癌增殖中的作用研究

项目名称： miR-92b、miR-181和miR-375调控网络靶向NLK在非小细胞肺癌增殖中的作用研究

项目编号： No.81460356

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李高峰

作者单位： 昆明医科大学

项目金额： 46万元

中文摘要： 云南宣威肺癌发病居全国首位，其发病机制远未阐明。新近研究表明，miRNA在肿瘤发生过程中起至关重要的作用。通过miRNA芯片我们在宣威NSCLC中发现miR-92b、miR-181和miR-375表达降低，软件预测：NLK是其共同作用靶点；进一步研究发现，在宣威肺癌细胞系XWLC-05导入上述miRNAs，NLK表达降低，细胞增殖能力下降, G1/S期阻滞，Cyclin D3表达降低；在宣威肺癌组织中，NLK与肿瘤大小密切相关，提示上述miRNAs靶向NLK调控CylinD3促进肺癌细胞增殖。由此，我们提出肺癌细胞增殖可能存在的信号转导机制：上述miRNAs调控网络靶向NLK调控Cyclin D3，促进NSCLC恶性增殖。本项目拟进一步用荧光素酶报告基因系统等技术，旨在获得上述miRNAs调控网络靶向NLK调控Cyclin D3促进NSCLC增殖的证据，阐明肺癌增殖信号转导通路作用机制。

中文关键词： miRNA；NLK；增殖；细胞周期；非小细胞肺癌

英文摘要： Xuanwei has the highest morbidity and mortality of lung cancer in China. However, the pathogenesis is still poorly understood. Recent investigations have demonstrated that miRNAs played a vital role in the process of tumorigenesis. Therefore, through a miRNA array with Xuanwei NSCLC tissues, we uncover miR-92b, miR-181 and miR-375 expression decreased. Bioinformatics analysis depicts the convergent targeting of the 3`UTRs of NLK by miR-92b, miR-181 and miR-375. Moreover we have identified that depression of these 3 miRNAs increases the expression of NLK. Meanwhile cell proliferation is significantly reduced , cell-cycle G1/S arrest and Cyclin D3 expression decreases in XWLC-05 cell line, which was derived from surgical resection tissue of a patient with lung cancer from Xuanwei. Notably, NLK expression was highly related with tumor volume in Xuanwei NSCLC tissues. Based on these results, we hypothesize that NLK mediated by a miRNA network leads to NSCLC cell abnormal proliferation. In this study, we further use Luciferase Assay and etc. to obtain reliable evidences on the hypothesis so as to identify the key target genes, and to provide a novel scientific proof for targeted therapy on NSCLC.

英文关键词： miRNA;NLK;Proliferation;cell cycle;NSCLC