miR-34 is associated with poor prognosis of patients with gallbladder cancer through regulating telomere length in tumor stem cells

Tumour Biol. 2014 Feb;35(2):1503-10. doi: 10.1007/s13277-013-1207-z.

Abstract

miR-34a has been identified as a tumor suppressor in several tumors, but its involvement in gallbladder cancer (GBC) has not been reported. In this study, the miR-34a level and telomere length were measured in 77 gallbladder adenocarcinomas and 36 peritumoral tissues by real-time PCR. Forced miR-34a expression was established by an adenovirus carrying a miR-34a expression cassette. The colony-forming ability of isolated CD44+CD133+ GBC tumor stem-like cells was measured by matrigel colony assay. The xenograft tumor models were established by inoculating nude mice with CD44+CD133+cells. Results showed that significantly lower miR-34a expression and longer telomere length were observed in gallbladder adenocarcinoma tissues, which correlated with poor prognosis of GBC patients. Forced overexpression of miR-34a inhibited the colony-forming ability of CD44+CD133+ GBC tumor stem-like cells in vitro and xenograft tumor growth in vivo. Injection of Ad-miR-34a downregulated PNUTS expression and reduced telomere length in xenograft GBC tumor cells. In conclusion, miR-34a is a tumor suppressor in gallbladder cancer. Both low miR-34a expression and long telomere length are markers for poor prognosis of patients with gallbladder adenocarcinoma. Our study also suggests that the miR-34a gene could be a target for targeting therapy of GBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Female
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplastic Stem Cells
  • Prognosis
  • Telomere Homeostasis / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN34 microRNA, human
  • MicroRNAs