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

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.