Background: We intended to investigate the role of microRNA 137 (miR-137) in regulating pancreatic cancer cells' growth in vitro and tumor development in vivo. Methods: QTR-PCR was used to examine the expression of miR-137 in pancreatic cancer cell lines and tumor cells from human patients. Lentivirual vector containing miR-137 mimic was used to overexpress miR-137 in PANC-1 and MIA PaCa-2 cells. The effects of overexpressing miR-137 on pancreatic cancer cell invasion and chemo-sensitivity to 5-fluorouracil (5-FU) were examined by cell migration and survival essays in vitro. The molecular target of miR-137, pleiotropic growth factor (PTN), was down-regulated by siRNA to examine its effects on cancer cell invasion. MIA PaCa-2 cells with endogenously overexpressed miR-137 were transplanted into null mice to examine tumor growth in vivo. Results: We found miR-137 was markedly under-expressed in both pancreatic cancer cell lines and tumor cells from patients. In cancer cells, transfection of lentivirus containing miR-137 mimic was able to markedly upregulate endogenous expression of miR-137, inhibited cancer cell invasion and increased sensitivities to chemotherapy reagent 5-FU. PTN was significantly down-regulated by overexpressing miR-137 in pancreatic cancer cells, and knocking down PTN was effective to rescue the reduced cancer cell invasion ability caused by miR-137 overexpression. More importantly, overexpressing miR-137 led to significant inhibition on tumor formation, including reductions in tumor weight and tumor size in vivo. Conclusion: Our study demonstrated that miR-137 played an important role in pancreatic cancer development. It may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer.
基金:
National Natural Science Foundation of China [81160311]; International Science Technology Cooperation Program of China [2014DFA31420]; Outstanding Young Training Project of Science and Education of Guizhou Province, China [[2012] 177]; China Postdoctoral Science Foundation [20-13M531983]
第一作者单位:[1]Guiyang Med Coll, Affiliated Hosp, Dept Hepatobiliary Surg, Guiyang 550004, Guizhou Provinc, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Xiao Jie,Peng Feng,Yu Chao,et al.microRNA-137 modulates pancreatic cancer cells tumor growth, invasion and sensitivity to chemotherapy[J].INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY.2014,7(11):7442-7450.
APA:
Xiao, Jie,Peng, Feng,Yu, Chao,Wang, Min,Li, Xu...&Sun, Chengyi.(2014).microRNA-137 modulates pancreatic cancer cells tumor growth, invasion and sensitivity to chemotherapy.INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY,7,(11)
MLA:
Xiao, Jie,et al."microRNA-137 modulates pancreatic cancer cells tumor growth, invasion and sensitivity to chemotherapy".INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 7..11(2014):7442-7450