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Tumor Biology

, Volume 35, Issue 2, pp 1503–1510 | Cite as

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

  • Ke Jin
  • Yonghua Xiang
  • Jing Tang
  • Guangchun Wu
  • Junwei Li
  • Huaichun Xiao
  • Chunwang Li
  • Yuxiang Chen
  • Jingfeng ZhaoEmail author
Research Article

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.

Keywords

Gallbladder cancer miR-34a Telomere length Prognosis 

Notes

Acknowledgments

This study was supported by the National Hi-tech Program (863 Project) of China (No. 2007AA021804, 2007AA021809).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Ke Jin
    • 1
  • Yonghua Xiang
    • 1
  • Jing Tang
    • 1
  • Guangchun Wu
    • 1
  • Junwei Li
    • 1
  • Huaichun Xiao
    • 1
  • Chunwang Li
    • 1
  • Yuxiang Chen
    • 2
  • Jingfeng Zhao
    • 2
    Email author
  1. 1.Department of RadiologyHunan Children’s HospitalChangshaChina
  2. 2.Hepatobiliary & Enteric Surgery Research Center, Xiangya HospitalCentral South UniversityChangshaChina

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