lncRNA RPPH1与非小细胞肺癌预后的分子流行病学研究

Lung cancer is one of the common malignancies worldwide. It’s observed that long noncoding RNA may play important roles in cancer progression. According to the TCGA database, RPPH1 is highly expressed in lung cancer samples. According to GEO database, RPPH1 is also upregulated in Chinese lung adenocarcinoma samples. High expression of RPPH1 is predictive of poor prognosis. Results of bioinformatics tools show that many genes are co-expressed genes of RPPH1, and these genes may play roles in pathways such as necroptosis, transcriptional misregulation in cancer according to GO and KEGG analysis. As predicted, up-frameshift protein-1 (UPF1) may be the RNA binding protein (RBP) of RPPH1. UPF1 is the key factor in nonsense-mediated mRNA decay (NMD), and the aberrant expression of UPF1 may promote the metastasis of cancer cells. Moreover, UPF1 may interact with the co-expressed genes of RPPH1. Based on these findings, we hypothesize that RPPH1 may influence lung cancer progression through UPF1/NMD pathway. So we plan to explore the predictive effect of RPPH1 on non-small cell lung cancer prognosis and the potential mechanism by conducting experiments in non-small cell lung cancer patients, cell lines and animal models. Our research may help to provide potential target for clinical treatment.

肺癌是严重影响人类健康的恶性肿瘤之一。长链非编码RNA在肺癌的发生、发展中发挥重要作用。TCGA数据库显示，RPPH1在肺癌组织中高表达，GEO芯片数据显示，RPPH1在中国人群肺腺癌组织中也高表达，且高表达提示预后不良。生物信息学分析结果显示RPPH1与较多基因存在共表达网络，GO和KEGG分析发现这些基因富集于凋亡、转录调控等肿瘤相关通路中。通过预测，发现上游移码蛋白-1（UPF1）可能是RPPH1的RNA结合蛋白。UPF1是无义介导的mRNA降解（NMD）途径的关键因子，其异常表达可促进肿瘤细胞的转移。且UPF1与RPPH1及其共表达基因存在相互作用网络。以上结果提示，RPPH1可能是通过UPF1介导的NMD途径影响肺癌的预后。因此本研究拟从人群、细胞、动物实验三个层面探讨异常表达的RPPH1与非小细胞肺癌预后的关系及其可能的作用机制，以期为临床治疗提供潜在的治疗靶点。

肺癌患者的5年存活期低，为了更好的提高肺癌患者的5年生存时间，寻找更有效的治疗靶点，本项目探讨非编码RNA RPPH1与非小细胞肺癌预后的研究。主要分析高表达RPPH1是否与非小细胞肺癌患者的预后有关，探讨高表达RPPH1对细胞和体外成瘤的影响，并通过多组学和单细胞测序的方法探讨可能的分子机制。经研究发现高表达RPPH1提示较差的预后，能提高肿瘤细胞的增殖能力，降低细胞的凋亡率，影响细胞周期，分子机制研究提示lgkc、AC0254191、SERPNE2、SFRP1、PPP1R14A和IGFBP6的依次下调可能是主要的原因。