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Upregulation of miR-1245 by c-myc targets BRCA2 and impairs DNA repair.
MedLine Citation:
PMID:  22158906     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BRCA2, a clinical prognostic factor, is significantly upregulated in mRNA level while its protein expression is often decreased in sporadic breast cancer. However, how BRCA2 protein expressions are suppressed in these tumors remains unknown. In this study, we demonstrated that miR-1245 directly suppressed BRCA2 3'-UTR and translation, impaired homologous recombination (HR)-mediated repair, reduced DNA damage-induced Rad51 nuclear foci and rendered cells hypersensitive to γ-irradiation (IR), ultimately inducing high chromosomal abnormalities in normal breast cells and breast cancer cells. Conversely, inhibiting miR-1245 in breast cancer cells enhanced BRCA2 levels and induced resistance to IR. Furthermore, we demonstrated that c-myc upregulated miR-1245 expression via direct binding to the miR-1245 promoter, which led to downregulation of BRCA2 and reduction of HR efficiency. Significantly, miR-1245 levels in primary breast tumors correlated with c-myc overexpression and BRCA2 suppression. These findings uncover a BRCA2 regulatory and signaling pathway in sporadic breast cancer and support a functionally and clinically relevant epigenetic mechanism in cancer pathogenesis.
Authors:
Libing Song; Ting Dai; Yingjun Xie; Chanjuan Wang; Chuyong Lin; Zhiqiang Wu; Zhe Ying; Jueheng Wu; Mengfeng Li; Jun Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-8
Journal Detail:
Title:  Journal of molecular cell biology     Volume:  -     ISSN:  1759-4685     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101503669     Medline TA:  J Mol Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
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