title: Down-regulation of miR-223 reverses epithelial-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells.
abstract: 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.
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China.|Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.
authors: Jia
authors: J
authors: Ma
authors: Research Center of Clinical Laboratory Science, Bengbu Medical College, Anhui 233030, China.
authors: Binbin
authors: B
authors: Fang
authors: Research Center of Clinical Laboratory Science, Bengbu Medical College, Anhui 233030, China.
authors: Fanpeng
authors: F
authors: Zeng
authors: Research Center of Clinical Laboratory Science, Bengbu Medical College, Anhui 233030, China.
authors: Cong
authors: C
authors: Ma
authors: Research Center of Clinical Laboratory Science, Bengbu Medical College, Anhui 233030, China.
authors: Haijie
authors: H
authors: Pang
authors: Department of Clinical Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241000, Anhui, China.
authors: Long
authors: L
authors: Cheng
authors: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.
authors: Ying
authors: Y
authors: Shi
authors: Research Center of Clinical Laboratory Science, Bengbu Medical College, Anhui 233030, China.
authors: Hui
authors: H
authors: Wang
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China.
authors: Bin
authors: B
authors: Yin
authors: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.
authors: Jun
authors: J
authors: Xia
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China.
authors: Zhiwei
authors: Z
authors: Wang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D035683:MicroRNAs; D000093542:Gemcitabine; C525067:MIR223, human
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