MicroRNA-223 Is Commonly Repressed in Hepatocellular Carcinoma and Potentiates Expression of Stathmin1
| Autor: | Queenie W. L. Wong, Priscilla T. Y. Law, Ka Fai To, Raymond W.M. Lung, Kathy Yuen Yee Chan, Nathalie Wong, Paul B.S. Lai |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Untranslated region Carcinoma Hepatocellular Hepatitis C virus Down-Regulation Biology medicine.disease_cause Hepatitis B Chronic microRNA medicine Humans Luciferase Luciferases Aged Oligonucleotide Array Sequence Analysis Regulation of gene expression Hepatitis B virus Hepatology Three prime untranslated region Liver Neoplasms Gastroenterology Hepatitis C Chronic Middle Aged medicine.disease Molecular biology digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs Hepatocellular carcinoma Stathmin Female |
| Zdroj: | Gastroenterology. 135:257-269 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2008.04.003 |
| Popis: | Background & Aims: Recent studies have emphasized causative links between microRNA (miRNA) deregulations and cancer development. In hepatocellular carcinoma (HCC), information on differentially expressed miRNA remained largely undefined. Methods: Array-based miRNA profiling was performed on HCC cells that were derived from chronic carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV), and nonviral-associated patients. Specific microRNA (miR)-223 and miR-222 deregulations were verified in an independent series of tumors. The functional effect of miR-223 was examined further. An integrative analysis of messenger RNA (mRNA) array with in silico predictions defined potential downstream targets of miR-223. A luciferase reporter assay was conducted to confirm target association. Results: Distinct up-regulations of miR-222, miR-221, and miR-31, and down-regulations of miR-223, miR-126, and miR-122a were identified. Further investigations suggested the highly deregulated miR-223 and miR-222 could unequivocally distinguish HCC from adjacent nontumoral liver, irrespective of viral associations ( P ≤ .0002). Re-expression of miR-223 in HBV, HCV, and non-HBV non-HCV–related HCC cell lines revealed a consistent inhibitory effect on cell viability ( P STMN1 ) as a downstream target of miR-223. A strong inverse relationship between STMN1 mRNA and miR-223 expressions was shown ( P = .006). A substantial reduction in STMN1 protein was further demonstrated upon restoration of miR-223 expression in HCC cell lines. We further showed that miR-223 readily could suppress the luciferase activity in reporter construct containing the STMN1 3' untranslated region ( P = .02). Conclusions: Our study revealed specific miRNA differential expressions in HCC and underscores the potential importance of miR-223 down-regulations in the development of HCC. |
| Databáze: | OpenAIRE |
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