MiR-205 functions as a tumor suppressor in adenocarcinoma and an oncogene in squamous cell carcinoma of esophagus

Tumour Biol. 2016 Jun;37(6):8007-18. doi: 10.1007/s13277-015-4656-8. Epub 2015 Dec 28.

Abstract

Esophageal cancer is a malignant disease with poor prognosis, increasing incidence, and ineffective treatment options. MicroRNAs are post-transcriptional regulators of gene expression involved in many biological processes including carcinogenesis. We determined miR-205 expression levels in tumor/non-tumor tissues of 45 esophageal cancer patients using qPCR and found that decreased level of miR-205 in tumor tissue correlates with poor overall survival in esophageal adenocarcinoma patients. Further, we observed significantly higher levels of miR-205 in tumor tissue of esophageal squamous cell carcinoma. Ectopic overexpression of miR-205 in adenocarcinoma cell line SK-GT-4 led to decreased cell proliferation, cell cycle arrest in G1, and decreased migration ability. Conversely, in squamous cell line KYSE-150, same effects like inhibition of proliferation, migration, and colony-forming potential and cell cycle arrest in G2 were observed after silencing of miR-205. We performed global gene expression profiling and revealed that suppressive functioning of miR-205 in adenocarcinoma could be realized through regulation of epithelial-mesenchymal transition (EMT), whereas oncogenic in squamous cell carcinoma by regulation of metalloproteinase 10. Our results suggest that miR-205 could serve as biomarker in esophageal cancer and acts as a tumor suppressor in esophageal adenocarcinoma and oncogene in esophageal squamous cell carcinoma.

Keywords: Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Oncogene; Tumor suppressor; miR-205.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / physiology
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • MicroRNAs / physiology*
  • Middle Aged
  • Oncogenes / genetics*
  • Real-Time Polymerase Chain Reaction
  • Survival Rate

Substances

  • MIRN205 microRNA, human
  • MicroRNAs

Supplementary concepts

  • Adenocarcinoma Of Esophagus