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Open Access Highly Accessed Methodology article

Discovery pipeline for epigenetically deregulated miRNAs in cancer: integration of primary miRNA transcription

Toby Hulf1, Tennille Sibbritt1, Erik D Wiklund12, Saul Bert1, Dario Strbenac1, Aaron L Statham1, Mark D Robinson13 and Susan J Clark14*

Author Affiliations

1 Epigenetics Laboratory, Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia

2 Department of Molecular Biology, Aarhus University, 8000 Aarhus C, Denmark

3 Bioinformatics Division, Walter and Eliza Hall of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia

4 St Vincent's Clinical School, University of NSW, St Vincent's Hospital, Darlinghurst, Sydney, 2010, New South Wales, Australia

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BMC Genomics 2011, 12:54  doi:10.1186/1471-2164-12-54

Published: 21 January 2011

Abstract

Background

Cancer is commonly associated with widespread disruption of DNA methylation, chromatin modification and miRNA expression. In this study, we established a robust discovery pipeline to identify epigenetically deregulated miRNAs in cancer.

Results

Using an integrative approach that combines primary transcription, genome-wide DNA methylation and H3K9Ac marks with microRNA (miRNA) expression, we identified miRNA genes that were epigenetically modified in cancer. We find miR-205, miR-21, and miR-196b to be epigenetically repressed, and miR-615 epigenetically activated in prostate cancer cells.

Conclusions

We show that detecting changes in primary miRNA transcription levels is a valuable method for detection of local epigenetic modifications that are associated with changes in mature miRNA expression.