title: Transforming growth factor‑β1 induces epithelial‑mesenchymal transition and increased expression of matrix metalloproteinase‑16 via miR‑200b downregulation in bladder cancer cells.
abstract: Transforming growth factor‑β1 (TGF‑β1) is involved in the migration and metastases of bladder cancer. The present study was designed to investigate whether TGF‑β1 is able to induce epithelial‑mesenchymal transition (EMT) and the upregulation of matrix metalloproteinase‑16 (MMP‑16), and to identify an association between EMT and MMP‑16 in bladder cancer. Following TGF‑β1 treatment, samples of HTB9 and T24 bladder cancer cells were collected at various time points. Western blotting and quantitative polymerase chain reaction (qPCR) confirmed that TGF‑β1 induced EMT in HTB9 and T24 cells at the protein and mRNA levels. The expression levels of the miR‑200 family were determined by qPCR, which indicated that TGF‑β1 treatment significantly reduced the expression of miR‑200b. Bioinformatic analysis indicated that MMP‑16 may be the target of miR‑200b. Reporter luciferase assay confirmed that MMP‑16 is a direct downstream functional target of miR‑200b. A Matrigel migration assay demonstrated that miR‑200b overexpression inhibited the migration of bladder cancer cells. In summary, the current study demonstrated that exogenous TGF‑β1 leads to the induction of EMT and the downregulation of miR‑200b in bladder cancer cells. To the best of our knowledge, this is the first evidence that MMP‑16 is a direct target of miR‑200b.
authors.affiliation: Department of Urology, Xiang Ya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Min Feng
authors.initials: MF
authors.lastname: Chen
authors.affiliation: Department of Urology, Xiang Ya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Department of Urology, Xiang Ya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Urology, Xiang Ya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiong Bing
authors.initials: XB
authors.lastname: Zu
authors.affiliation: Department of Urology, First Teaching Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Xiang Ya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Long Fei
authors.initials: LF
authors.lastname: Liu
authors.affiliation: Department of Urology, Xiang Ya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019295:Computational Biology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D053513:Matrix Metalloproteinase 16 / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C533896:MIRN200 microRNA, human; C507102:MMP16 protein, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D053513:Matrix Metalloproteinase 16