miRNA Gene Promoters Are Frequent Targets of Aberrant DNA Methylation in Human Breast Cancer
- University of Arizona, Tucson, AZ (United States); Biology Centre ASCR v.v.i., Ceske Budejovice (Czech Republic); DOE/OSTI
- University of Arizona, Tucson, AZ (United States)
- University of Arizona, Tucson, AZ (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Life Sciences Division
miRNAs are important regulators of gene expression that are frequently deregulated in cancer, with aberrant DNA methylation being an epigenetic mechanism involved in this process. We previously identified miRNA promoter regions active in normal mammary cell types and here we analyzed which of these promoters are targets of aberrant DNA methylation in human breast cancer cell lines and breast tumor specimens. Using 5-methylcytosine immunoprecipitation coupled to miRNA tiling microarray hybridization, we performed comprehensive evaluation of DNA methylation of miRNA gene promoters in breast cancer. We found almost one third (55/167) of miRNA promoters were targets for aberrant methylation in breast cancer cell lines. Breast tumor specimens displayed DNA methylation of majority of these miRNA promoters, indicating that these changes in DNA methylation might be clinically relevant. Aberrantly methylated miRNA promoters were, similar to protein coding genes, enriched for promoters targeted by polycomb in normal cells. Detailed analysis of selected miRNA promoters revealed decreased expression of miRNA linked to increased promoter methylation for mir-31, mir-130a, let-7a-3/let-7b, mir-155, mir-137 and mir-34b/mir-34c genes. The proportion of miRNA promoters we found aberrantly methylated in breast cancer is several fold larger than that observed for protein coding genes, indicating an important role of DNA methylation in miRNA deregulation in cancer.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- Margaret E. and Fenton L. Maynard Endowment for Breast Cancer Research; National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1627580
- Journal Information:
- PLoS ONE, Journal Name: PLoS ONE Journal Issue: 1 Vol. 8; ISSN 1932-6203
- Publisher:
- Public Library of ScienceCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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