MicroRNA Expression and Identification of Putative miRNA Targets in Ovarian Cancer

Abstract

BackgroundMicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Emerging evidence suggests the potential involvement of altered regulation of miRNA in the pathogenesis of cancers, and these genes are thought to function as both tumor suppressors and oncogenes.Methodology/Principal FindingsUsing microRNA microarrays, we identify several miRNAs aberrantly expressed in human ovarian cancer tissues and cell lines. miR-221 stands out as a highly elevated miRNA in ovarian cancer, while miR-21 and several members of the let-7 family are found downregulated. Public databases were used to reveal potential targets for the highly differentially expressed miRNAs. In order to experimentally identify transcripts whose stability may be affected by the differentially expressed miRNAs, we transfected precursor miRNAs into human cancer cell lines and used oligonucleotide microarrays to examine changes in the mRNA levels. Interestingly, there was little overlap between the predicted and the experimental targets or pathways, or between experimental targets/pathways obtained using different cell lines, highlighting the complexity of miRNA target selection.Conclusion/SignificanceOur results identify several differentially expressed miRNAs in ovarian cancer and identify potential target transcripts that may be regulated by these miRNAs. These miRNAs and their targets may have important roles in the initiation and development of ovarian cancer.

MicroRNA-30c-2* Expressed in Ovarian Cancer Cells Suppresses Growth Factor–Induced Cellular Proliferation and Downregulates the Oncogene BCL9

“…For this we downloaded an expression dataset (GSE10150, N ¼ 45; ref. 23) from the NCBI Entrez Gene Expression Omnibus (GEO) DataSets website and assessed miR-30c among the specimens. Although miR-30c-2 Ã was not included in the dataset, we observed a significant range in expression of miR-30c among high-grade serous epithelial ovarian carcinoma (Fig.…”

“…23) was downloaded from the NCBI Entrez Gene Expression Omnibus (GEO) DataSets website (http://www. ncbi.nlm.nih.gov/sites/entrez?db¼gds) and analyzed as previously described (10).…”

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

“…In silico expression and comparative genomic hybridisation analyses Dysregulated miRNAs in ovarian cancer was compiled from eight published studies (Iorio et al, 2007;Bearfoot et al, 2008;Dahiya et al, 2008;Nam et al, 2008;Taylor and Gercel-Taylor, 2008;Zhang et al, 2008;Boren et al, 2009;Resnick et al, 2009). Assessment of KLK protein dysregulation in ovarian cancer was compiled from the results of 17 studies (Dong et al, 2001;Luo et al, 2001Luo et al, , 2003Tanimoto et al, 2001;Hoffman et al, 2002;Yousef et al, , 2003bBorgono et al, 2003;Diamandis et al, 2003;Ni et al, 2004;Scorilas et al, 2004;Xi et al, 2004;Prezas et al, 2006;Shan et al, 2007;Bayani et al, 2008;Shaw and Diamandis, 2008).…”

miRNA analysis of formalin-fixed squamous cell carcinomas of the tongue is affected by age of the samples

“…A novel finding was the consistent upregulation of miR-424 in tumour samples. Upregulation of this miRNA has not been seen before in SCC of the head and neck but has been implicated in a number of malignancies including ovarian cancer (29), non-small cell lung carcinoma (30) and kidney cancer (31). One potential miR-424 target, ITGAV, has previously been seen to significantly correlate with differentiation and metastasis in laryngeal and hypopharyngeal carcinomas (29,32).…”