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

被引：57
作者：
Hulf, Toby [1 ]
Sibbritt, Tennille [1 ]
Wiklund, Erik D. [1 ,2 ]
Bert, Saul [1 ]
Strbenac, Dario [1 ]
Statham, Aaron L. [1 ]
Robinson, Mark D. [1 ,4 ]
Clark, Susan J. [1 ,3 ]
机构：
[1] Garvan Inst Med Res, Canc Res Program, Epigenet Lab, Darlinghurst, NSW 2010, Australia
[2] Aarhus Univ, Dept Mol Biol, DK-8000 Aarhus C, Denmark
[3] Univ NSW, St Vincents Hosp, St Vincents Clin Sch, Darlinghurst, NSW 2010, Australia
[4] Walter & Eliza Hall Med Res, Bioinformat Div, Parkville, Vic 3052, Australia
来源：
BMC GENOMICS | 2011年 / 12卷
基金：
澳大利亚国家健康与医学研究理事会;
关键词：
PROSTATE-CANCER; DNA METHYLATION; POSTTRANSCRIPTIONAL REGULATION; MICRORNA EXPRESSION; HUMAN GENOME; HYPERMETHYLATION; MIR-196B; CELLS; CHROMATIN; NETWORK;
D O I：
10.1186/1471-2164-12-54
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
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.
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页数：9
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