title: miR-15b promotes epithelial-mesenchymal transition by inhibiting SMURF2 in pancreatic cancer.
abstract: The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We report here that silencing SMURF2 (SMAD specific E3 ubiquitin protein ligase 2) promoted EMT in HPDE6c7 normal pancreas cells and overexpression of SMURF2 inhibited TGF-β-mediated EMT in the cells. Subsequent studies showed that SMURF2 was downregulated in pancreatic cancer tissues and it promoted mesenchymal-epithelial transition (MET) in pancreatic cancer cells as well as its expression negatively associated with gemcitabine-resistance, but it did not alter cell viability, cell cycle and cell senescence. In addition, we demonstrated that miR‑15b degraded SMURF2 and its overexpression promoted EMT in pancreatic cancer, and its expression was associated with metastasis in the disease. Elucidating molecular mechanism of EMT in pancreatic cancer not only will help us to further understand the pathogenesis and progression of the disease, but also offers new targets for effective therapies.
authors.affiliation: Department of General Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
authors.forename: Xi-Zhao
authors.initials: XZ
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Hepatobiliary Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
mesh_terms: D002460:Cell Line; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D003841:Deoxycytidine; C471641:SMURF2 protein, human; D044767:Ubiquitin-Protein Ligases; D000093542:Gemcitabine