RT Journal Article
SR Electronic
T1 MicroRNA Expression Profiling in Human Ovarian Cancer: <em>miR-214</em> Induces Cell Survival and Cisplatin Resistance by Targeting <em>PTEN</em>
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 425
OP 433
DO 10.1158/0008-5472.CAN-07-2488
VO 68
IS 2
A1 Yang, Hua
A1 Kong, William
A1 He, Lili
A1 Zhao, Jian-Jun
A1 O'Donnell, Joshua D.
A1 Wang, Jiawang
A1 Wenham, Robert M.
A1 Coppola, Domenico
A1 Kruk, Patricia A.
A1 Nicosia, Santo V.
A1 Cheng, Jin Q.
YR 2008
UL http://cancerres.aacrjournals.org/content/68/2/425.abstract
AB 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] ©2008 American Association for Cancer Research.