MiR-126 promotes esophageal squamous cell carcinoma via inhibition of apoptosis and autophagy

Aging (Albany NY). 2020 Jun 18;12(12):12107-12118. doi: 10.18632/aging.103379. Epub 2020 Jun 18.

Abstract

MiRNA-126 (miR-126) has been shown to be involved in various malignancies as well as other biological processes. However, currently, its role in esophageal squamous cell carcinoma (ESCC) is not well understood. The present study is focused on the mechanisms that underlie the effect of miR-126 on cell survival and death (apoptosis and autophagy) in ESCC cells. MiR-126 expression was found to be enhanced in ESCC cells and tissues. Downregulation of miR-126 suppressed cell survival, and TUNEL staining indicated that miR-126 inhibition promoted ESCC cell death. In addition, the production of LC3B and p62 proteins, two autophagy signals, was reduced following miR-126 inhibition. A dual luciferase reporter assay demonstrated that the STAT3 3'-UTR is a direct target of miR-126. Furthermore, STAT3 knock-down rescued the effects on autophagy and apoptosis caused by miR-126 inhibition in ESCC cells. The results of this study may provide some insight into the molecular and biological mechanisms underlying ESCC generation and contribute to the development of novel therapeutic approaches for ESCC.

Keywords: STAT3; apoptosis; autophagy; esophageal squamous cell carcinoma; miR-126.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Autophagy / drug effects
  • Autophagy / genetics
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Esophageal Squamous Cell Carcinoma / surgery
  • Esophagectomy
  • Esophagus / pathology
  • Esophagus / surgery
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • STAT3 Transcription Factor / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN126 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human