MicroRNA‑34a Inhibits Esophageal Squamous Cell Carcinoma Progression by Targeting E2F5

J BUON. Nov-Dec 2019;24(6):2514-2522.

Abstract

Purpose: Previous studies have explored the role of microRNA-34a (miR-34a) and E2F transcription family in several tumors, however, the expression level and oncogenesis mechanism of these two factors in esophageal squamous cancer cells (ESCC) remains unclear. Our study aims to explore the inhibitory effect of miR-34a in ESCC as well as its downstream factor E2F5.

Methods: We explored the relevant expression level of miR-34a in human tumor tissue as well as in several ESCC cell lines. Through RNA mimic and inhibitor, we examined the specific role of miR-34a in the proliferation, apoptosis and migration of tumor cells, and we further explored the role of downstream factor E2F5 through gain- and loss-of-function analyses.

Results: We found that the expression level of miR-34a is significantly downregulated in ESCC tissues as well as in ESCC cell lines, and miR-34a plays an inhibitory role in tumor cell proliferation and migration while it promotes tumor cell apoptosis. We further showed that E2F5 is a direct functional target of miR-34a, as it promotes tumor cell proliferation and migration and inhibits apoptosis.

Conclusions: Our results indicate that the intrinsic expression of miR-34a was relatively low in ESCC. The anti-tumor effect of miR-34a is possibly dependent on the regulation of cell-cycle regulator E2F5.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Disease Progression
  • E2F5 Transcription Factor / genetics
  • E2F5 Transcription Factor / metabolism*
  • 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*
  • Humans
  • MicroRNAs / genetics*
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • E2F5 Transcription Factor
  • E2F5 protein, human
  • MIRN34 microRNA, human
  • MicroRNAs