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miRNA Gene Promoters Are Frequent Targets of Aberrant DNA Methylation in Human Breast Cancer

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [2]
  1. University of Arizona, Tucson, AZ (United States); Biology Centre ASCR v.v.i., Ceske Budejovice (Czech Republic); DOE/OSTI
  2. University of Arizona, Tucson, AZ (United States)
  3. 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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Cited By (38)

Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment journal April 2015
microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration and Comparative Analysis journal December 2017
MethHC: a database of DNA methylation and gene expression in human cancer journal November 2014
Inhibition of transforming growth factor beta/ SMAD signal by MiR‐155 is involved in arsenic trioxide‐induced anti‐angiogenesis in prostate cancer journal November 2014
Detection of Differentially Expressed MicroRNAs in Rheumatic Heart Disease: miR-1183 and miR-1299 as Potential Diagnostic Biomarkers journal January 2015
Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells journal July 2014
Effect of cigarette smoke condensate on gene promoter methylation in human lung cells journal January 2014
Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors journal January 2013
MicroRNA-31 controls G protein alpha-13 (GNA13) expression and cell invasion in breast cancer cells journal March 2015
A novel mechanism of regulation of the anti-metastatic miR-31 by EMSY in breast cancer journal November 2014
Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori journal December 2019
miR-599 Inhibits Vascular Smooth Muscle Cells Proliferation and Migration by Targeting TGFB2 journal November 2015
Aberrant methylation-mediated silencing of microRNAs contributes to HPV-induced anchorage independence journal May 2016
An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization journal December 2019
MicroRNA‑34b promotes proliferation, migration and invasion of Ewing's sarcoma cells by downregulating Notch1 journal August 2018
Human papilloma virus, DNA methylation and microRNA expression in cervical cancer (Review) journal April 2014
Additional file 1 of Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation dataset January 2020
Additional file 2 of Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation dataset January 2020
Additional file 3 of Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation dataset January 2020
Additional file 4 of Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation dataset January 2020
A Combination of DNA-peptide Probes and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): A Quasi-Targeted Proteomics Approach for Multiplexed MicroRNA Quantification journal January 2017
miRNA and Methylation: A Multifaceted Liaison journal December 2014
Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery: Chemopreventive role of olive oil in colon carcinogenesis journal October 2018
MicroRNA epigenetic signatures in human disease journal August 2016
Marker Systems Based on MicroRNA Gene Methylation for the Diagnosis of Stage I-II Breast Cancer journal November 2019
MicroRNA-411 promoted the osteosarcoma progression by suppressing MTSS1 expression journal February 2018
miR-99a and -99b inhibit cervical cancer cell proliferation and invasion by targeting mTOR signaling pathway journal March 2014
Epigenetics: spotlight on type 2 diabetes and obesity journal May 2016
DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2 journal October 2014
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MicroRNA modulators of epigenetic regulation, the tumor microenvironment and the immune system in lung cancer journal January 2015
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Новые гены микроРНК, гиперметилированные при раке молочной железы journal January 2016

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