Document Detail

MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease.
MedLine Citation:
PMID:  18949056     Owner:  NLM     Status:  MEDLINE    
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.
Seung-Ok Lee; Tatyana Masyuk; Patrick Splinter; Jesús M Banales; Anatoliy Masyuk; Angela Stroope; Nicholas Larusso
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-23
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  118     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-04     Completed Date:  2009-01-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3714-24     Citation Subset:  AIM; IM    
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
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MeSH Terms
Bile Ducts / metabolism
Cell Line
Disease Models, Animal*
Liver Diseases / metabolism*
MicroRNAs / metabolism*
Polycystic Kidney, Autosomal Recessive / genetics,  metabolism*
Rats, Sprague-Dawley
cdc25 Phosphatases / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/MicroRNAs; 0/mirn15 microRNA, rat; EC protein, rat; EC Phosphatases
Comment In:
J Clin Invest. 2008 Nov;118(11):3585-7   [PMID:  18949060 ]

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