LncRNA PRR11-AS1通过PRR11及p53通路调控细胞增殖与凋亡影响肺腺癌预后的分子机制研究

肺癌是我国最常见的恶性肿瘤，肺腺癌约占肺癌总数的一半，影响其预后机制尚未完全阐明。已有多种长链非编码RNA（lncRNA）被发现与肺腺癌预后存在相关性。本课题组通过生物信息学挖掘，发现肺腺癌患者癌组织中lncRNA PRR11-AS1与生存密切相关，其后在临床样本中证实lncRNA-PRR11-AS1在肺腺癌组织中高表达，转染lncRNA-PRR11-AS1慢病毒表达载体可以促进肺腺癌细胞的增殖同时抑制细胞凋亡，使p53通路相关蛋白Noxa、Bax、Puma及p21的表达显著下调。因此，我们提出假说“lncRNA-PRR11-AS1可以调控p53通路，影响肺腺癌细胞增殖与凋亡，参与预后过程”。在预实验的基础上，本课题拟在细胞模型中通过细胞转染、免疫沉淀技术等实验方法，深入探讨其在肺腺癌预后进程中的作用及相关分子机制，为肺腺癌的治疗寻找新的分子靶点。

Lung cancer is the most common malignant tumor in China, in which lung adenocarcinoma accounts for about 50% lung cancer in total. The prognostic mechanism affecting it has not been fully elucidated. A variety of long non-coding RNAs (lncRNAs) have been found to be associated with lung adenocarcinoma survival. We found that lncRNA PRR11-AS1 is associated with lung adenocarcinoma patient’s survival by bioinformatics data mining. By measuring lncRNA PRR11-AS1 expression in clinical samples, we confirmed that the high expression of lncRNA PRR11-AS1 in lung adenocarcinoma tissue. The overexpression of lncRNA PRR11-AS1 could promote lung adenocarcinoma cell proliferation and inhibit cell apoptosis. Further experiments showed that overexpression of lncRNA PRR11-AS1 could decrease the expressions of p53 downstream target genes including Noxa, Bax, Puma and p21. We propose the following hypothesis: "lncRNA PRR11-AS1 can regulate p53 pathway, affecting the proliferation and apoptosis of lung adenocarcinoma cells, and can participate in the prognostic process of lung adenocarcinoma". On the basis of pre-experiment, this project intends to understand the molecular mechanisms that how lncRNA PRR11-AS1 regulates lung adenocarcinoma cells by cell transfection, co-immunoprecipitation, and other experimental methods, which provides new molecular targets for the treatment of lung adenocarcinoma.