Huo Zhen, Zhai Shuyu, Weng Yuanchi, Qian Hao, Tang Xiaomei, Shi Yusheng, Deng Xiaxing, Wang Yue, Shen Baiyong
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Onco Targets Ther. 2019 Jun 28;12:5037-5051. doi: 10.2147/OTT.S206039. eCollection 2019.
Pre-mRNA processing factor 40 homolog A (PRPF40A) is an important protein involved in pre-mRNA splicing and is expressed in a variety of cell types. However, the function of PRPF40A in pancreatic cancer remains unclear. Therefore, our study is to investigate the role of PRPF40A in the pathogenesis of pancreatic cancer.
We extracted expression data and clinical information of PRPF40A from different online databases, including the Cancer Genome Atlas (TCGA), Oncomine and the Gene Expression Omnibus (GEO). Subsequently, samples were collected from patients to validate gene expression using qPCR, Western blotting and immunohistochemical (IHC) analyses. Receiver operating characteristic (ROC) and Kaplan-Meier curve were used to evaluate the diagnostic and prognostic potential. Colony formation assays and CCK-8 assays were performed to measure the proliferative capacity of pancreatic cancer. Finally, gene ontology (GO) and pathway enrichment analyses of co-expressed genes of PRPF40A were conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID).
We found that PRPF40A was upregulated based on data from both the online databases and our samples. PRPF40A possessed a significant diagnostic value, and its overexpression was associated with poor prognosis. PRPF40A knockdown inhibited cell proliferation in pancreatic cancer. GO and pathway analysis showed that the co-expressed genes were mainly involved in viral processing, mRNA splicing and the AMPK signaling pathway.
The results suggest that PRPF40A is an oncogene and can serve as a diagnostic and prognostic biomarker for pancreatic cancer. However, the underlying mechanisms remain to be elucidated.
前体mRNA加工因子40同源物A(PRPF40A)是一种参与前体mRNA剪接的重要蛋白质,在多种细胞类型中表达。然而,PRPF40A在胰腺癌中的功能仍不清楚。因此,我们的研究旨在探讨PRPF40A在胰腺癌发病机制中的作用。
我们从不同的在线数据库中提取了PRPF40A的表达数据和临床信息,包括癌症基因组图谱(TCGA)、Oncomine和基因表达综合数据库(GEO)。随后,从患者中收集样本,使用qPCR、蛋白质免疫印迹和免疫组织化学(IHC)分析来验证基因表达。采用受试者工作特征(ROC)曲线和Kaplan-Meier曲线评估其诊断和预后潜力。进行集落形成试验和CCK-8试验以测量胰腺癌的增殖能力。最后,使用注释、可视化和综合发现数据库(DAVID)对PRPF40A的共表达基因进行基因本体(GO)和通路富集分析。
我们发现,基于在线数据库和我们的样本数据,PRPF40A均上调。PRPF40A具有显著的诊断价值,其过表达与不良预后相关。敲低PRPF40A可抑制胰腺癌细胞增殖。GO和通路分析表明,共表达基因主要参与病毒加工、mRNA剪接和AMPK信号通路。
结果表明,PRPF40A是一种癌基因,可作为胰腺癌的诊断和预后生物标志物。然而,其潜在机制仍有待阐明。