BACKGROUND/AIMS: MicroRNAs (miRNAs) play critical roles during carcinogenesis and cancer progression. Down-regulation of miR-204 has been frequently observed in various cancers. In this study, we investigated the roles and mechanisms of miR-204 in human intrahepatic cholangiocarcinoma (ICC). METHODS: The relative expression of miR-204 in ICC tissues and cell lines was monitored by qRT-PCR. Effects of miR-204 were studied in human ICC cell lines HuH28 and HuCCT1, and cells were analyzed for proliferation, migration and invasion. Expression levels of miR-204 target gene Slug and EMT markers (E-cadherin and vimentin) in ICC cell lines and tissues were measured by qRT-PCR, western blotting and immunofluorescence. RESULTS: miR-204 was frequently downregulated in human ICC, and the low-level expression of miR-204 was significantly associated with lymph node metastasis. Overexpression of miR-204 dramatically suppressed ICC cell migration and invasion, as well as the epithelial-mesenchymal transition process (EMT). Slug was identified as a direct target of miR-204, and its downregulation by miR-204 in HuH28 cells reversed EMT, as shown by the increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker vimentin. CONCLUSION: These findings suggest that miR-204 plays negative roles in the invasive and/or metastatic potential of ICC, and that its suppressive effects are mediated by repressing Slug expression.
BACKGROUND/AIMS: MicroRNAs (miRNAs) play critical roles during carcinogenesis and cancer progression. Down-regulation of miR-204 has been frequently observed in various cancers. In this study, we investigated the roles and mechanisms of miR-204 in humanintrahepatic cholangiocarcinoma (ICC). METHODS: The relative expression of miR-204 in ICC tissues and cell lines was monitored by qRT-PCR. Effects of miR-204 were studied in human ICC cell lines HuH28 and HuCCT1, and cells were analyzed for proliferation, migration and invasion. Expression levels of miR-204 target gene Slug and EMT markers (E-cadherin and vimentin) in ICC cell lines and tissues were measured by qRT-PCR, western blotting and immunofluorescence. RESULTS:miR-204 was frequently downregulated in human ICC, and the low-level expression of miR-204 was significantly associated with lymph node metastasis. Overexpression of miR-204 dramatically suppressed ICC cell migration and invasion, as well as the epithelial-mesenchymal transition process (EMT). Slug was identified as a direct target of miR-204, and its downregulation by miR-204 in HuH28 cells reversed EMT, as shown by the increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker vimentin. CONCLUSION: These findings suggest that miR-204 plays negative roles in the invasive and/or metastatic potential of ICC, and that its suppressive effects are mediated by repressing Slug expression.
Authors: Valeria Canu; Andrea Sacconi; Laura Lorenzon; Francesca Biagioni; Federica Lo Sardo; Maria Grazia Diodoro; Paola Muti; Alfredo Garofalo; Sabrina Strano; Antonietta D'Errico; Gian Luca Grazi; Mario Cioce; Giovanni Blandino Journal: Oncotarget Date: 2017-05-02
Authors: Sergio A Gradilone; Steven P O'Hara; Tetyana V Masyuk; Maria Jose Lorenzo Pisarello; Nicholas F LaRusso Journal: Semin Liver Dis Date: 2015-01-29 Impact factor: 6.115
Authors: Melina M Musri; Núria Coll-Bonfill; Bradley A Maron; Víctor I Peinado; Rui-Sheng Wang; Jordi Altirriba; Isabel Blanco; William M Oldham; Olga Tura-Ceide; Jessica García-Lucio; Benjamin de la Cruz-Thea; Gunter Meister; Joseph Loscalzo; Joan A Barberà Journal: Am J Respir Cell Mol Biol Date: 2018-10 Impact factor: 6.914