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Cancer Research 68, 425, January 15, 2008. doi: 10.1158/0008-5472.CAN-07-2488
© 2008 American Association for Cancer Research
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Molecular Biology, Pathobiology, and Genetics

MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN

Hua Yang, William Kong, Lili He, Jian-Jun Zhao, Joshua D. O'Donnell, Jiawang Wang, Robert M. Wenham, Domenico Coppola, Patricia A. Kruk, Santo V. Nicosia and Jin Q. Cheng

Departments of Interdisciplinary Oncology and Pathology, H. Lee Moffitt Cancer Center and Research Institute and University of South Florida College of Medicine, Tampa, Florida

Requests for reprints: Jin Q. Cheng, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, SRB3, Tampa, FL 33612. Phone: 813-745-6915; Fax: 813-745-3928; E-mail: jin.cheng{at}moffitt.org.

MicroRNAs (miRNA) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers. However, aberrant miRNA expression and its clinicopathologic significance in human ovarian cancer have not been well documented. Here, we show that several miRNAs are altered in human ovarian cancer, with the most significantly deregulated miRNAs being miR-214, miR-199a*, miR-200a, miR-100, miR-125b, and let-7 cluster. Further, we show the frequent deregulation of miR-214, miR-199a*, miR-200a, and miR-100 in ovarian cancers. Significantly, miR-214 induces cell survival and cisplatin resistance through targeting the 3'-untranslated region (UTR) of the PTEN, which leads to down-regulation of PTEN protein and activation of Akt pathway. Inhibition of Akt using Akt inhibitor, API-2/triciribine, or introduction of PTEN cDNA lacking 3'-UTR largely abrogates miR-214–induced cell survival. These findings indicate that deregulation of miRNAs is a recurrent event in human ovarian cancer and that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway. [Cancer Res 2008;68(2):425–33]




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
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Copyright © 2008 by the American Association for Cancer Research.