Zhong Xiaowu, Huang Guangcheng, Ma Qiang, Liao Hebin, Liu Chang, Pu Wenjie, Xu Lei, Cai Yan, Guo Xiaolan
Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College.
Translational Medicine Research Center.
Medicine (Baltimore). 2019 Jul;98(27):e16269. doi: 10.1097/MD.0000000000016269.
Esophageal squamous cell carcinoma (ESCC) is a malignancy that severely threatens human health and carries a high incidence rate and a low 5-year survival rate. MicroRNAs (miRNAs) are commonly accepted as a key regulatory function in human cancer, but the potential regulatory mechanisms of miRNA-mRNA related to ESCC remain poorly understood.The GSE55857, GSE43732, and GSE6188 miRNA microarray datasets and the gene expression microarray datasets GSE70409, GSE29001, and GSE20347 were downloaded from Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using GEO2R. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network and functional modules were established using the STRING database and were visualized by Cytoscape. Kaplan-Meier analysis was constructed based on The Cancer Genome Atlas (TCGA) database.In total, 26 DEMs and 280 DEGs that consisted of 96 upregulated and 184 downregulated genes were screened out. A functional enrichment analysis showed that the DEGs were mainly enriched in the ECM-receptor interaction and cytochrome P450 metabolic pathways. In addition, MMP9, PCNA, TOP2A, MMP1, AURKA, MCM2, IVL, CYP2E1, SPRR3, FOS, FLG, TGM1, and CYP2C9 were considered to be hub genes owing to high degrees in the PPI network. MiR-183-5p was with the highest connectivity target genes in hub genes. FOS was predicted to be a common target gene of the significant DEMs. Hsa-miR-9-3p, hsa-miR-34c-3p and FOS were related to patient prognosis and higher expression of the transcripts were associated with a poor OS in patients with ESCC.Our study revealed the miRNA-mediated hub genes regulatory network as a model for predicting the molecular mechanism of ESCC. This may provide novel insights for unraveling the pathogenesis of ESCC.
食管鳞状细胞癌（ESCC）是一种严重威胁人类健康的恶性肿瘤，其发病率高且5年生存率低。微小RNA（miRNA）在人类癌症中通常被认为具有关键的调节功能，但与ESCC相关的miRNA-mRNA潜在调节机制仍知之甚少。从基因表达综合数据库下载了GSE55857、GSE43732和GSE6188 miRNA微阵列数据集以及基因表达微阵列数据集GSE70409、GSE29001和GSE20347。使用GEO2R获得差异表达的miRNA（DEM）和差异表达的基因（DEG）。通过注释、可视化和综合发现数据库（DAVID）对DEG进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。使用STRING数据库建立蛋白质-蛋白质相互作用（PPI）网络和功能模块，并通过Cytoscape进行可视化。基于癌症基因组图谱（TCGA）数据库构建Kaplan-Meier分析。
总共筛选出26个DEM和280个DEG，其中包括96个上调基因和184个下调基因。功能富集分析表明，DEG主要富集于细胞外基质-受体相互作用和细胞色素P450代谢途径。此外，由于在PPI网络中具有较高的度数，MMP9、PCNA、TOP2A、MMP1、AURKA、MCM2、IVL、CYP2E1、SPRR3、FOS、FLG、TGM1和CYP2C9被认为是枢纽基因。MiR-183-5p在枢纽基因中具有最高连接性的靶基因。FOS被预测为重要DEM的共同靶基因。Hsa-miR-9-3p、hsa-miR-34c-3p和FOS与患者预后相关，转录本的高表达与ESCC患者的不良总生存期相关。
我们的研究揭示了miRNA介导的枢纽基因调控网络作为预测ESCC分子机制的模型。这可能为阐明ESCC的发病机制提供新的见解。
