MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis
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Jianwei Xu1,*, Tianxiao Wang2,*, Zhe Cao1, Hua Huang1, Jian Li1, Wenjing Liu1, Shanglong Liu1, Lei You1, Li Zhou1, Taiping Zhang1, Yupei Zhao1
1 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of head and neck Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
* These authors contributed equally to this work
Taiping Zhang , email:
Yupei Zhao , email:
Keywords: pancreatic cancer, miRNA, chemoresistance, prognosis
Received: May 06, 2014 Accepted: July 06, 2014 Published: July 08, 2014
Chemoresistance is one of the causes of poor prognosis in pancreatic cancer patients. However, the mechanisms of resistance remain unclear. Here we screened miRNAs associated with drug resistance in pancreatic cancer, and identified a panel of miRNAs dysregulated in gemcitabine-resistance pancreatic cancer cells, including 13 downregulated miRNAs and 20 upregulated miRNAs. Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples (P=0.000). Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer (P=0.01, hazard ratio=2.762, 95% confidence interval: 1.159–6.579). Together these results indicate that miR-497 could be a new therapeutic target and prognostic marker of pancreatic cancer.
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