Molecular pathogenesis of esophageal squamous cell carcinoma: Identification of the antitumor effects of miR‑145‑3p on gene regulation

Int J Oncol. 2019 Feb;54(2):673-688. doi: 10.3892/ijo.2018.4657. Epub 2018 Dec 6.

Abstract

Although miR‑145‑5p (the guide strand of the miR‑145 duplex) is established as a tumor suppressive microRNA (miRNA or miR), the functional significance of miR‑145‑3p (the passenger strand of the miR‑145 duplex) in cancer cells and its targets remains obscure. In our continuing analysis of esophageal squamous cell carcinoma (ESCC) pathogenesis, the aim of the present study was to identify important oncogenes and proteins that are controlled by miR‑145‑3p. Overexpression of miR‑145‑3p significantly reduced cancer cell proliferation, migration and invasive abilities, and further increased apoptotic abilities. In ESCC cells, 30 possible oncogenic targets were identified that might be regulated by miR‑145‑3p. Among these targets, dehydrogenase/reductase member 2 (DHRS2) and myosin IB (MYO1B) were focused on to investigate their functional roles in ESCC cells. DHRS2 and MYO1B were directly regulated by miR‑145‑3p in ESCC cells by dual luciferase reporter assays. Aberrantly expressed DHRS2 and MYOIB were detected in ESCC clinical specimens, and their overexpression enhanced cancer cell aggressiveness. Genes regulated by antitumor miR‑145‑3p were closely associated with the molecular pathogenesis of ESCC. The approach based on antitumor miRNAs may contribute to the understanding of ESCC molecular pathogenesis.

Keywords: microRNA; passenger strand; microRNA-145-3p; esophageal squamous cell carcinoma; dehydrogenase/reductase member 2; myosin IB.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Oxidoreductases / genetics*
  • Carbonyl Reductase (NADPH)
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / genetics
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Myosin Type I / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Nuclear Proteins / genetics*
  • RNA Interference

Substances

  • MIRN145 microRNA, human
  • MYO1B protein, human
  • MicroRNAs
  • Nuclear Proteins
  • Alcohol Oxidoreductases
  • Carbonyl Reductase (NADPH)
  • DHRS2 protein, human
  • Myosin Type I