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.
Ke
K
Jin
Yonghua
Y
Xiang
Jing
J
Tang
Guangchun
G
Wu
Junwei
J
Li
Huaichun
H
Xiao
Chunwang
C
Li
Yuxiang
Y
Chen
Jingfeng
J
Zhao
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D014411:Neoplastic Stem Cells; D011379:Prognosis; D059505:Telomere Homeostasis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
C522425:MIRN34 microRNA, human; D035683:MicroRNAs