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Biochem Biophys Res Commun. 2011 Jan 28;404(4):896-902. doi: 10.1016/j.bbrc.2010.12.055. Epub 2010 Dec 15.

miR-181a shows tumor suppressive effect against oral squamous cell carcinoma cells by downregulating K-ras.

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  • 1School of Dentistry, University of California, Los Angeles, CA 90095, USA. kshin@dentistry.ucla.edu

Abstract

MicroRNAs (miRNAs) are epigenetic regulators of gene expression, and their deregulation plays an important role in human cancer, including oral squamous cell carcinoma (OSCC). Recently, we found that miRNA-181a (miR-181a) was upregulated during replicative senescence of normal human oral keratinocytes. Since senescence is considered as a tumor suppressive mechanism, we thus investigated the expression and biological role of miR-181a in OSCC. We found that miR-181a was frequently downregulated in OSCC. Ectopic expression of miR-181a suppressed proliferation and anchorage independent growth ability of OSCC. Moreover, miR-181a dramatically reduces the growth of OSCC on three dimensional organotypic raft culture. We also identified K-ras as a novel target of miR-181a. miR-181a decreased K-ras protein level as well as the luciferase activity of reporter vectors containing the 3'-untranslated region of K-ras gene. Finally, we defined a minimal regulatory region of miR-181a and found a positive correlation between its promoter activity and the level of miR-181a expression. In conclusion, miR-181a may function as an OSCC suppressor by targeting on K-ras oncogene. Thus, miR-181a should be considered for therapeutic application for OSCC.

Published by Elsevier Inc.

PMID:
21167132
[PubMed - indexed for MEDLINE]
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