基于生物信息学数据库分析IER2在肿瘤中高表达及其作用机制

Upregulation of IER2 and Its Mechanism Analysis in Tumor Based on Bioinformatics Database

人即刻早期反应基因2(immediate early response 2,IER2)可能参与肿瘤的发生发展,但它在此过程中的作用及表达调控的机制仍不清楚。本研究通过在线数据库GEPIA2与Kaplan-Meier Plotter分析发现:TNF和IER2基因在食管癌组织和宫颈癌组织中高表达。而且IER2基因高表达的食管癌病人的预后显著较差。通过UCSC基因组数据库分析发现,在宫颈癌细胞和淋巴细胞内,TNFα(由TNF基因编码)诱导激活NF-κB结合IER2基因区。qRT-PCR检测证明,在食管癌和宫颈癌等细胞内,TNFα诱导NF-κB在转录水平上调IER2基因的表达。本文据此提出,TNFα诱导NF-κB上调IER2基因的表达可能是其在食管癌和宫颈癌等肿瘤中高表达的调控机制。本研究还通过在线数据库GeneMANIA和String分析发现11个与IER2具有关联性的基因。通过在线数据库Oncomine分析发现了88个基因在食管癌细胞内与IER2基因共表达。其中,包含7个与IER2具有关联性的基因ATF3、DUSP1、EGR1、EGR2、FOSB、JUN、NR4A1。本研究通过Oncomine数据库分析证明,在前列腺癌组织细胞内,这7个基因也与IER2共表达。并通过qRT-PCR检测验证这7个基因在食管癌细胞内与IER2基因共表达。GO注释表明,IER2可能通过与ATF3、EGR1、JUN相互作用,协同参与细胞增殖等生物学过程。CCK8检测证明,IER2基因过表达促进食管癌细胞生长增殖。总之,本研究初步揭示了IER2在食管癌和宫颈癌中高表达的调控机制及其作用,为深入研究该基因功能提供了线索。

Immediate early response 2(IER2) is involved in the progression of tumors. However, the mechanisms of its regulation and role are not clear in this process. In this study, an on-line database GEPIA2 showed that TNF and IER2 were highly expressed in esophageal cancer and cervical cancer tissues. Moreover, Kaplan-Meier Plotter showed that the prognosis of esophageal cancer patients with high-expression of IER2 gene was significantly poorer as compared with the low expression group. Analysis of UCSC genomic database showed that the binding of NF-κB to IER2 was induced by TNFα in cervical cancer cells and lymphocytes. qRT-PCR assay showed that TNFα upregulated expression of IER2 gene by NF-κB signal pathway at transcriptional level in cancer cells, such as esophageal and cervical cancer cells. Therefore, it is proposed that the up-regulation of IER2 gene by TNFα-activated NF-κB as a molecular mechanism for its high-expression in esophageal and cervical cancer. In addition, the on-line database GeneMANIA and String showed that there were 11 IER2-related genes(IRGs). Oncomine database analysis showed co-expression of 88 genes with IER2 gene in esophageal cancer cells. Among them, ATF3, DUSP1, EGR1, EGR2, FOSB, JUN, and NR4A1 were IRGs. The seven IRGs were also co-expressed with IER2 gene in prostate cancer tissues analyzed by Oncomine database. qRT-PCR assay confirmed co-expression of the seven IRGs with IER2 gene in esophageal cancer cells. Gene ontology annotation indicated that IER2 participated in cell proliferation and other biological processes through these IRGs including ATF3, EGR1 and JUN. CCK8 assay showed that overexpression of IER2 promoted the growth and proliferation of esophageal cancer cells. In conclusion, this study preliminarily showed a mechanism of IERs high expression and its role in esophageal and cervical cancer, which may provide new clues for further study of IER2 function.