miRNA-lncRNA网络调控eIF3a基因的表达及其在肺癌铂类化疗耐药中的作用及机制研究

进展期肺癌化疗主要以铂类药物为主，但疗效和毒副反应的个体反应差异很大。我们前期研究发现 eIF3a基因及其多态性通过调控DNA修复酶表达来调节肺癌铂类药物化疗的敏感性。在此基础上，本研究通过双荧光素酶报告基因及基因转染等技术，进一步查明miR-26a，miR-26b和miR-186以及具有内源性竞争作用的６种lncRNAs (AC058791.2，CTD-2314B22.3，AL589743.1；RP11-218M22.1，PVT1，DCP1A) 如何调控eIF3a基因的表达，同时阐明上述miRNAs-lncNAs与肺癌铂类药物化疗敏感性及预后的相关性，最后明确这些miRNA-lncRNA网络影响肺癌铂类化疗耐药及预后的分子机制。本课题旨在从表观遗传学及ceRNA假说角度为肺癌铂类药物化疗耐药的发生提供全新的解释机制，为进一步阐明eIF3a作为肺癌个体化治疗新的分子靶标提供科学依据。

Cisplatin is the basic chemotherapy in advanced lung cancer, but there are large individual differences in the chemotherapy efficacy and side -effect of platinum-based drugs. Our previous studies found that eIF3a gene and its polymorphisms could regulate sensitivity of platinum- based chemotherapy in lung cancer patients by changing the activities of DNA repair enzymes. Based on these works, we try to further identify the relationship between the miR-26a, miR-26b, miR-186 and the lncRNAs (AC058791.2，CTD-2314B22.3，AL589743.1；RP11-218M22.1，PVT1，DCP1A) with endogenous competitive and the expression of eIF3a gene. At the same time, we will further elucidate the interaction of miRNA-lncRNA how to regulate the expression of eIF3a gene and their effections and possible molecular mechanism of resistance to platinum-based chemotherapy in patients with lung cancer. The aim of this study is probably going to provides a new explanation and give a further understanding of the eIF3a action in platinum-based drugs resistance in lung cancer from the perspective of epigenetics and ceRNA hypothesis, and provide some new scientific evidences in eIF3a and miRNA or lncRNA as a molecular target for personalized pharmacotherapy of lung cancer.