Abstract：Objective: To screen the differentially expressed miRNAs(DE-miRNAs) associated with the esophageal squamous cell carcinoma (ESCC) and to analyze their biological functions by using various bioinformatics analysis tools. Methods: The expression profiles of GSE114110 were downloaded from the Gene Expression Omnibus (GEO) database; GEO2R tool was used to analyze the data and to screen DE-miRNAs; The miRNA expression profiles of esophageal squamous cell carcinoma (GSE97049, GSE59973, GSE55856 and GSE43732 )were used to verify the selected DE-miRNAs; the potential target genes were predicted by miRNet ; DAVID was introduced to perform functional annotation and pathway enrichment analysis for these potential targets of DE-miRNAs; String and Cytoscape were used to construct protein-protein interaction (PPI) network and identify the key Hub genes, and further to construct miRNA-Hub gene network; the expression of Hub genes were verified by the starBase analysis tool. Results: A total of 159 DE-miRNAs were screened out, including 86 upregulated miRNAs and 73 downregulated miRNAs in ESCC tissues compared with normal esophageal epithelia. 1700 target genes of the top three upregulated and downregulated miRNAs were predicted, and they were involved in ESCC-related pathways, such as pathway in cancer, focal adhesion and p53 signaling pathway. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as MAPK1. Through constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by hsa-miR-196a-5p and hsa-miR-1. The expression of target gene (CDC42,POLR2K,PIK3CA,POLR2I,HIST2H2AC,FN1,VEGFA) of hsa-miR-1 was significantly upregulated in ESCC tissue than normal tissue. There is an inverse relationship between miRNA expression and target gene expression. Thus, these significantly upregulated genes including CDC42,POLR2K,PIK3CA,POLR2I,HIST2H2AC,FN1 and VEGFA may be the most potential targets for the downregulated hsa-miR-1 in theory. Conclusion: Through bioinformatics analysis of the differentially expressed miRNAs between esophageal squamous cell carcinoma tissues and normal epithelial tissues, two DE-miRNAs and seven key hub genes were finally screened to provide theoretical guidance for further research on molecular marker screening and molecular mechanisms of ESCC.
[1] Hu C, Peng J, Lv L, et al. miR-196a regulates the proliferation, invasion and migration of esophageal squamous carcinoma cells by targeting ANXA1[J]. Oncology Letters,2019,17:5201~5209. [2] Fendereski M, Zia MF, Shafiee M, et al.MicroRNA-196a as a potential diagnostic biomarker for esophageal squamous cell carcinoma[J].Cancer Invest,2017,35:78~84. [3] Liu W, Li M, Chen X, et al. MicroRNA-1 suppresses proliferation, migration and invasion by targeting Notch2 in esophageal squamous cell carcinoma[J].Scientific Reports, 2018,8:5183. [4] Du Y-Y, Zhao L-M, Chen L, et al. The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in esophageal squamous cell carcinoma[J].Journal of Gastroenterology and Hepatology,2016,31:384~393. [5] Xiao J, Yang W, Xu B, et al. Expression of fibronectin in esophageal squamous cell carcinoma and its role in migration[J].BMC Cancer,2018,18:976. [6] Wei Q, Li X, Yu W, et al. microRNA-messenger RNA regulatory network of esophageal squamous cell carcinoma and the identification of miR-1 as a biomarker of patient survival[J].Cell Biochem,2019,120:12259~12272. [7] Noorolyai S, Shajari N, Baghbani E, et al.The relation between PI3K/AKT signalling pathway and cancer[J].Gene,2019,698:120~128. [8] Yu Q, Liu Y, Wen C, et al. MicroRNA-1 inhibits tumorigenicity of esophageal squamous cell carcinoma and enhances sensitivity to gefitinib[J].Oncology Letters,2018,15:963~971. [9] Chou J, Wang B, Zheng T, et al. MALAT1 induced migration and invasion of human breast cancer cells by competitively binding miR-1 with cdc42[J].Biochemical and Biophysical Research Communications,2016,472:262~269. [10] Xie M, Dart DA, Guo T, et al. MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer[J].Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association,2018,21:41~54.
2020, Vol. 26 
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