MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN
| Autor: | Santo V. Nicosia, Robert M. Wenham, Domenico Coppola, William Kong, Patricia A. Kruk, Jin Q. Cheng, Jian-jun Zhao, Hua Yang, Lili He, Joshua D. O'Donnell, Jia-Wang Wang |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Tumor suppressor gene Cell Survival Molecular Sequence Data Antineoplastic Agents Apoptosis Bioinformatics Sequence Homology Nucleic Acid microRNA Tumor Cells Cultured medicine Humans PTEN Gene silencing miR-214 Protein kinase B PI3K/AKT/mTOR pathway Oligonucleotide Array Sequence Analysis Ovarian Neoplasms Base Sequence biology Gene Expression Profiling PTEN Phosphohydrolase Cancer medicine.disease Gene Expression Regulation Neoplastic Oncogene Protein v-akt MicroRNAs Oncology Drug Resistance Neoplasm biology.protein Cancer research Female Ribonucleosides Cisplatin Signal Transduction |
| Zdroj: | Cancer Research. 68:425-433 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-07-2488 |
| Popis: | 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] |
| Databáze: | OpenAIRE |
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