Using the Exiqon microRNA microarrays, we have identified 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. The transcripts that were most significantly altered by miRNA overexpression contained binding sites for the corresponding miRNAs. Interestingly, there was little overlap between the predicted and the experimental targets, or between experimental targets obtained using different cell lines highlighting the complexity of miRNA target selection. We are currently investigating the targets of these miRNAs in order to clarify their roles in ovarian cancer. This work involves the validation of the targets by RT-PCR in cell lines and tissues, as well as the expression of these targets in ovarian cells to functionally test their functions.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Institute on Aging
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Dahiya, Neetu; Morin, Patrice J (2010) MicroRNAs in ovarian carcinomas. Endocr Relat Cancer 17:F77-89
Lal-Nag, Madhu; Morin, Patrice J (2009) The claudins. Genome Biol 10:235
Choi, Jung-Hye; Park, Joon T; Davidson, Ben et al. (2008) Jagged-1 and Notch3 juxtacrine loop regulates ovarian tumor growth and adhesion. Cancer Res 68:5716-23