Down-regulation of miR-223 reverses epithelial-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells
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Jia Ma1,2, Binbin Fang3, Fanpeng Zeng3, Cong Ma3, Haijie Pang3, Long Cheng4, Ying Shi2, Hui Wang3, Bin Yin1, Jun Xia2, Zhiwei Wang1
1The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China
2Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China
3Research Center of Clinical Laboratory Science, Bengbu Medical College, Anhui 233030, China
4Department of Clinical Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241000, Anhui, China
Zhiwei Wang, e-mail: [email protected]
Jun Xia, e-mail: [email protected]
Bin Yin, e-mail: [email protected]
Keywords: Gemcitabine, miR-223, EMT, invasion, pancreatic cancer
Received: October 01, 2014 Accepted: November 08, 2014 Published: December 31, 2014
Recent studies have demonstrated that acquisition of epithelial-to-mesenchymal transition (EMT) is associated with drug resistance in pancreatic cancer cells; however, the underlying mechanisms are not fully elucidated. Emerging evidence suggests that microRNAs play a crucial role in controlling EMT. The aims of this study were to explore the potential role of miR-223 in governing EMT in gemcitabine-resistant (GR) pancreatic cancer cells. To achieve this goal, real-time reverse transcription-PCR and western blot analysis were used to validate whether GR cells acquired EMT in AsPC-1 and PANC-1 cells. Invasion, migration, and detachment assays were performed to further identify the EMT characteristics in GR cells. The miR-223 inhibitor was used to determine its role in GR-induced EMT. We found that GR cells acquired EMT features, which obtained elongated fibroblastoid morphology, decreased expression of epithelial marker E-cadherin, and up-regulation of mesenchymal markers. Furthermore, we observed that GR cells are associated with high expression of miR-223. Notably, inhibition of miR-223 led to the reversal of EMT phenotype. More importantly, miR-223 governs GR-induced EMT in part due to down-regulation of its target Fbw7 and subsequent upregulation of Notch-1 in pancreatic cancer. Our study implied that down-regulation of miR-223 could be a novel therapy for pancreatic cancer.
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