Abstract
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.
Highlights
Pancreatic cancer is a lethal disease, with a 5-year survival rate of less than 5% [1]
Screening miRNAs associated with drug resistance in pancreatic cancer
To identify miRNAs associated with drug resistance in pancreatic cancer, we screened the miRNA expression profile in parental SW1990 and gemcitabine-resistant SW1990 (SW1990/GEM) cells using Illumina miRNA arrays
Summary
Pancreatic cancer is a lethal disease, with a 5-year survival rate of less than 5% [1]. One of the reasons underlying poor prognosis of pancreatic cancer is drug resistance. Gemcitabine is a first line chemotherapeutic agent that is widely used for treatment of advanced pancreatic cancer. Only 9.4% of patients with metastatic pancreatic cancers achieve partial response, and 34.5% show a progressive disease during the chemotherapy [2]. Newer therapeutic regimens and some targeted therapies, such as epidermal growth factor receptor tyrosine kinase inhibitor, are superior to conventional regimens, but the overall survival is still unsatisfactory [3, 4]. Determining the mechanisms of drug resistance and re-sensitizing pancreatic cancer cells to chemotherapy are essential measures for improving survival
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