| MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. | |
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MedLine Citation:
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PMID: 18949056 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hyperproliferation of bile duct epithelial cells due to cell-cycle dysregulation is a key feature of cystogenesis in polycystic liver diseases (PCLDs). Recent evidence suggests a regulatory role for microRNAs (miRNAs) in a variety of biological processes, including cell proliferation. We therefore hypothesized that miRNAs may be involved in the regulation of selected components of the cell cycle and might contribute to hepatic cystogenesis. We found that the cholangiocyte cell line PCK-CCL, which is derived from the PCK rat, a model of autosomal recessive polycystic kidney disease (ARPKD), displayed global changes in miRNA expression compared with normal rat cholangiocytes (NRCs). More specific analysis revealed decreased levels of 1 miRNA, miR15a, both in PCK-CCL cells and in liver tissue from PCK rats and patients with a PCLD. The decrease in miR15a expression was associated with upregulation of its target, the cell-cycle regulator cell division cycle 25A (Cdc25A). Overexpression of miR15a in PCK-CCL cells decreased Cdc25A levels, inhibited cell proliferation, and reduced cyst growth. In contrast, suppression of miR15a in NRCs accelerated cell proliferation, increased Cdc25A expression, and promoted cyst growth. Taken together, these results suggest that suppression of miR15a contributes to hepatic cystogenesis through dysregulation of Cdc25A. |
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Authors:
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Seung-Ok Lee; Tatyana Masyuk; Patrick Splinter; Jesús M Banales; Anatoliy Masyuk; Angela Stroope; Nicholas Larusso |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-10-23 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 118 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-04 Completed Date: 2009-01-12 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 3714-24 Citation Subset: AIM; IM |
Affiliation:
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Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile Ducts / metabolism Cell Line Disease Models, Animal* Humans Liver Diseases / metabolism* MicroRNAs / metabolism* Polycystic Kidney, Autosomal Recessive / genetics, metabolism* Rats Rats, Sprague-Dawley cdc25 Phosphatases / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK24031/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/MicroRNAs; 0/mirn15 microRNA, rat; EC 3.1.3.48/Cdc25a protein, rat; EC 3.1.3.48/cdc25 Phosphatases |
| Comments/Corrections | |
Comment In:
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J Clin Invest. 2008 Nov;118(11):3585-7
[PMID:
18949060
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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