Bioinformatics-based analysis of the lncRNA-miRNA-mRNA and TF regulatory networks reveals functional genes in esophageal squamous cell carcinoma

Biosci Rep. 2020 Aug 28;40(8):BSR20201727. doi: 10.1042/BSR20201727.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a 5-year survival rate unsatisfied malignancies. The study aimed to identify the novel diagnostic and prognostic targets for ESCC. Expression profiling (GSE89102, GSE97051, and GSE59973) data were downloaded from the GEO database. Then, differentially expressed (DE) lncRNAs, DEmiRNAs, and genes (DEGs) with P-values < 0.05, and |log2FC| ≥ 2, were identified using GEO2R. Functional enrichment analysis of miRNA-related mRNAs and lncRNA co-expressed mRNA was performed. LncRNA-miRNA-mRNA, protein-protein interaction of miRNA-related mRNAs and DEGs, co-expression, and transcription factors-hub genes network were constructed. The transcriptional data, the diagnostic and prognostic value of hub genes were estimated with ONCOMINE, receiver operating characteristic (ROC) analyses, and Kaplan-Meier plotter, respectively. Also, the expressions of hub genes were assessed through qPCR and Western blot assays. The CDK1, VEGFA, PRDM10, RUNX1, CDK6, HSP90AA1, MYC, EGR1, and SOX2 used as hub genes. And among them, PRDM10, RUNX1, and CDK6 predicted worse overall survival (OS) in ESCC patients. Our results showed that the hub genes were significantly up-regulated in ESCA primary tumor tissues and cell lines, and exhibited excellent diagnostic efficiency. These results suggest that the hub genes may server as potential targets for the diagnosis and treatment of ESCC.

Keywords: Bioinformatics; DEGs; Esophageal squamous cell carcinoma; MicroRNAs; Prognosis; ceRNA; core genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Computational Biology*
  • Databases, Genetic
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / mortality
  • Esophageal Squamous Cell Carcinoma / pathology
  • Esophageal Squamous Cell Carcinoma / therapy
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics*
  • Prognosis
  • Protein Interaction Maps
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • Transcription Factors / genetics*
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • Transcription Factors