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Molecular Biology, Pathobiology, and Genetics |
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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Correction: miRNA Profiling in Ovarian Cancer and miR-214 Targets PTEN Cancer Res., March 1, 2008; 68(5): 1609 - 1609. [Full Text] [PDF]
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