Hypoxia-regulated MicroRNAs in Gastroesophageal Cancer

Anticancer Res. 2016 Feb;36(2):721-30.


Background/aim: The present study aimed to identify hypoxia-regulated microRNAs (HRMs) in vitro and investigate the clinical role of candidate HRMs in patients with gastroesophageal cancer (GEC).

Materials and methods: microRNA expression changes induced by hypoxia in human GEC cell lines were measured with microarrays and validated by quantitative real-time polymerase chain reaction. Candidate HRMs were measured in pre-therapeutic tumor samples from 195 patients with GEC.

Results: Expression of miR-210 was shown to be significantly induced in esophageal squamous cell carcinoma (9.26-fold, p<0.001) and adenocarcinoma cell lines (4.95-fold, p<0.001) and miR-27a-star was significantly up-regulated in adenocarcinoma cell lines (4.79-fold, p=0.04). A weak but significant correlation between miR-210 expression and a 15-gene hypoxia signature was observed (Pearson r correlation: r=0.38, p<0.001). No significant associations of HRMs and clinical outcome in patients with GEC were identified.

Conclusion: This study supports the involvement of hypoxia on miRNAs in vitro and confirms the role of miR-210 as being a universal HRM.

Keywords: Gastroesophageal cancer; hypoxia; miRNA-210; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Cell Hypoxia
  • Cell Line, Tumor
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Proportional Hazards Models
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Treatment Outcome


  • MIRN210 microRNA, human
  • MicroRNAs

Supplementary concepts

  • Adenocarcinoma Of Esophagus