MicroRNA-182-5-p targets a network of genes involved in DNA repair

Krishnan, Keerthana, Steptoe, Anita L., Martin, Hilary C., Wani, Shivangi, Nones, Katia, Waddell, Nic, Mariasegaram, Mythily, Simpson, Peter T., Lakhani, Sunil R., Gabrielli, Brian, Vlassov, Alexander, Cloonan, Nicole and Grimmond, Sean M. (2013) MicroRNA-182-5-p targets a network of genes involved in DNA repair. RNA, 19 2: 230-242. doi:10.1261/rna.034926.112

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Author Krishnan, Keerthana
Steptoe, Anita L.
Martin, Hilary C.
Wani, Shivangi
Nones, Katia
Waddell, Nic
Mariasegaram, Mythily
Simpson, Peter T.
Lakhani, Sunil R.
Gabrielli, Brian
Vlassov, Alexander
Cloonan, Nicole
Grimmond, Sean M.
Title MicroRNA-182-5-p targets a network of genes involved in DNA repair
Journal name RNA   Check publisher's open access policy
ISSN 1355-8382
1469-9001
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.1261/rna.034926.112
Open Access Status File (Publisher version)
Volume 19
Issue 2
Start page 230
End page 242
Total pages 13
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2013
Language eng
Abstract MicroRNAs are noncoding regulators of gene expression, which act by repressing protein translation and/or degrading mRNA. Many have been shown to drive tumorigenesis in cancer, but functional studies to understand their mode of action are typically limited to single-target genes. In this study, we use synthetic biotinylated miRNA to pull down endogenous targets of miR-182-5p. We identified more than 1000 genes as potential targets of miR-182-5p, most of which have a known function in pathways underlying tumor biology. Specifically, functional enrichment analysis identified components of both the DNA damage response pathway and cell cycle to be highly represented in this target cohort. Experimental validation confirmed that miR-182-5p-mediated disruption of the homologous recombination (HR) pathway is a consequence of its ability to target multiple components in that pathway. Although there is a strong enrichment for the cell cycle ontology, we do not see primary proliferative defects as a consequence of miR-182-5p overexpression. We highlight targets that could be responsible for miR-182-5p-mediated disruption of other biological processes attributed in the literature so far. Finally, we show that miR-182-5p is highly expressed in a panel of human breast cancer samples, highlighting its role as a potential oncomir in breast cancer.
Keyword PARP inhibition
Biotin pull-down
miRNA
Target identification
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published in Advance December 18, 2012

 
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Created: Thu, 17 Jan 2013, 12:09:28 EST by Susan Allen on behalf of Institute for Molecular Bioscience