MicroRNA‑200a promotes esophageal squamous cell carcinoma cell proliferation, migration and invasion through extensive target genes

Mol Med Rep. 2020 May;21(5):2073-2084. doi: 10.3892/mmr.2020.11002. Epub 2020 Feb 26.

Abstract

Despite investigations into microRNA (miRNA) expression in esophageal cancer (EC) tissue, miRNAs that participate in EC pathogenesis and their subsequent mechanisms of action remain to be determined. The present study aimed to identify important miRNAs that contribute to EC development, and to assess miRNA biomarkers that could be used in EC diagnosis, prognosis and therapy. Bioinformatics analysis was performed to reanalyze EC tissue miRNA expression microarray dataset GSE113776, which was followed by in vitro verification of miRNA functions using reverse transcription‑quantitative PCR, western blot analysis and a dual‑luciferase reporter assay. Out of 93 miRNAs extracted, only miR‑200a was significantly increased in EC tissues. Transfection of KYSE150 esophageal squamous cell carcinoma (ESCC) cells with miR‑200a mimics significantly increased their proliferative, migratory and invasive ability, whereas the opposite cell behaviors were observed in ESCC cells transfected with a miR‑200a inhibitor. A total of six miR‑200a target genes [catenin β1 (CTNNB1), cadherin‑1 (CDH1), PTEN, adenomatous polyposis coli (APC), catenin α1 (CTNNA1) and superoxide dismutase 2 (SOD2)] were selected for further analysis based on Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein‑protein interaction network map data and protein expression in esophageal tissue. These target genes were downregulated under miR‑200a expression and upregulated in the presence of the miR‑200a inhibitor. The association between miR‑200a and the 3'‑untranslated region of target genes in ESCC cells was confirmed using a dual‑luciferase reporter assay. In conclusion, the present study demonstrated that miR‑200a may participate in the promotion of ESCC cell proliferation, migration and invasion, and provided novel evidence for the direct interaction between miR‑200a and CTNNB1, CDH1, PTEN, APC, CTNNA1 and SOD2, which may contribute to the observed altered cell behavior.

Keywords: microrna-200a; esophageal cancer; esophageal squamous cell carcinoma; cell behaviors; bioinformatics.

MeSH terms

  • 3' Untranslated Regions
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Computational Biology
  • Down-Regulation
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Ontology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Protein Interaction Maps
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Up-Regulation
  • alpha Catenin / genetics
  • alpha Catenin / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • 3' Untranslated Regions
  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • MIRN200 microRNA, human
  • MicroRNAs
  • alpha Catenin
  • beta Catenin
  • Superoxide Dismutase
  • superoxide dismutase 2
  • PTEN Phosphohydrolase
  • PTEN protein, human