miR-204 Inhibits Epithelial to Mesenchymal Transition by Targeting Slug in Intrahepatic Cholangiocarcinoma Cells
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2013-11-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/354531 |
| Summary: | 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. |
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| ISSN: | 1015-8987 1421-9778 |