miR-204 Inhibits Epithelial to Mesenchymal Transition by Targeting Slug in Intrahepatic Cholangiocarcinoma Cells

Autor: Zhouchong Wang, Yongjie Zhang, Wenlong Yu, Ning-jia Shen, Yongpeng Wei, Qiu Yinghe, Kan Tong, Bin Yi
Rok vydání: 2013
Předmět:
Zdroj: Cellular Physiology and Biochemistry, Vol 32, Iss 5, Pp 1331-1341 (2013)
ISSN: 1421-9778
1015-8987
DOI: 10.1159/000354531
Popis: 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.
Databáze: OpenAIRE