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 |
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Rok vydání: | 2013 |
Předmět: |
Male
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Physiology Slug Down-Regulation Vimentin medicine.disease_cause lcsh:Physiology lcsh:Biochemistry Cholangiocarcinoma Cell Movement Cell Line Tumor microRNA medicine Humans lcsh:QD415-436 Epithelial–mesenchymal transition Intrahepatic cholangiocarcinoma Cell Proliferation Regulation of gene expression lcsh:QP1-981 biology Cadherin Liver Neoplasms EMT miR-204 Cell migration Middle Aged Cadherins biology.organism_classification Gene Expression Regulation Neoplastic MicroRNAs Bile Ducts Intrahepatic Bile Duct Neoplasms biology.protein Cancer research Snail Family Transcription Factors Carcinogenesis Transcription Factors |
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 |
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