Discovery pipeline for epigenetically deregulated miRNAs in cancer: integration of primary miRNA transcription.
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.
Epigenetics Laboratory, Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
Toby
T
Hulf
Tennille
T
Sibbritt
Erik D
ED
Wiklund
Saul
S
Bert
Dario
D
Strbenac
Aaron L
AL
Statham
Mark D
MD
Robinson
Susan J
SJ
Clark
D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*
D035683:MicroRNAs
PLoS One. 2010 Feb 25;5(2):e9429
20195546
Oncogene. 2002 Feb 7;21(7):1048-61
11850822
Mol Cell. 2010 May 14;38(3):323-32
20471939
Oncogene. 2008 Mar 13;27(12):1788-93
17891175
Nat Rev Cancer. 2010 May;10(5):361-71
20357775
Haematologica. 2010 Oct;95(10):1675-82
20494936
Int J Cancer. 2009 Dec 1;125(11):2737-43
19521961
Hum Genet. 2007 Jan;120(5):701-11
17024368
Int J Cancer. 2011 Mar 15;128(6):1327-34
20473948
Clin Cancer Res. 2010 Feb 15;16(4):1129-39
20145181
Int J Biochem Cell Biol. 2009 Jan;41(1):87-95
18834952
Genes Dev. 2006 Aug 15;20(16):2202-7
16882971
Blood. 2008 Feb 1;111(3):1217-26
17957028
Int J Cancer. 2011 Jan 1;128(1):132-43
20309880
Genome Res. 2010 Dec;20(12):1719-29
21045081
Int J Cancer. 2010 Sep 1;127(5):1072-80
20039318
Cancer Res. 2003 May 1;63(9):2164-71
12727835
Mol Cancer. 2010 Jan 21;9:12
20092645
Nature. 2004 May 27;429(6990):457-63
15164071
Int J Cancer. 2010 Mar 1;126(5):1166-76
19676045
Cell Cycle. 2010 Mar 1;9(5):923-9
20160498
Nat Cell Biol. 2010 Mar;12(3):235-46
20173741
Cell Cycle. 2006 Jan;5(2):155-8
16397413
BMC Cancer. 2009 Nov 18;9:401
19922656
Cancer Res. 2007 Sep 15;67(18):8699-707
17875710
PLoS One. 2009 Nov 13;4(11):e7826
19915715
Curr Opin Cell Biol. 2009 Jun;21(3):470-9
19411171
Nat Rev Genet. 2008 Oct;9(10):789-96
18781158
Blood. 2009 Apr 2;113(14):3314-22
19188669
Genes Chromosomes Cancer. 2010 Nov;49(11):969-80
20662076
Br J Cancer. 2009 Jan 27;100(2):240-5
19002169
Cancer Res. 2009 Mar 15;69(6):2287-95
19244118
Nucleic Acids Res. 2010 Jan;38(2):391-9
19906696
Int J Cancer. 2007 Mar 1;120(5):1046-54
17149698
PLoS One. 2009;4(3):e4687
19262738
PLoS One. 2010 Jan 13;5(1):e8697
20084174
Int J Cancer. 2010 Jun 1;126(11):2553-62
19830692
Cell. 2009 Jun 12;137(6):1032-46
19524507
Pathology. 2007 Jun;39(3):299-304
17558856
Stat Appl Genet Mol Biol. 2004;3:Article3
16646809
Epigenomics. 2010 Dec;2(6):823-40
22122085
Clin Chem. 2009 Apr;55(4):623-31
19246618
Am J Pathol. 2010 May;176(5):2113-30
20348243
Cancer Res. 2004 Jun 1;64(11):3871-7
15172996
RNA. 2008 Jan;14(1):35-42
18025253