BRCA2,a clinical prognostic factor,is significantly up-regulated in mRNA level,while its protein expression is often decreased in sporadic breast cancer.However,how BRCA2 protein expressions are suppressed in these tu...BRCA2,a clinical prognostic factor,is significantly up-regulated 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 BRCA23′-UTR and translation,impaired homologous recombination(HR)-mediated repair,reduced DNA damage-induced Rad51 nuclear foci,and rendered cells hypersensitive to g-irradiation(IR),ul-timately 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 up-regulated miR-1245 expression via direct binding to the miR-1245 promoter,which led to down-regulation of BRCA2 and reduction in 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.展开更多
The immunohistochemistry(IHC)staining of MID2 in“ANT”from Patient 2 and“T”from Patient 6 in original Fig.2C(Page 45)should be corrected.The authors apologize for this error and state that this does not change the ...The immunohistochemistry(IHC)staining of MID2 in“ANT”from Patient 2 and“T”from Patient 6 in original Fig.2C(Page 45)should be corrected.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.展开更多
基金supported by the National Natural Science Foundation of China (Nos.81071647,81071762,30872930,81071780,81030048,30870963,and 30831160517)the Science and Technology Department of Guangdong Province,China (No.S2011020002757)the Fundamental Research Funds for the Central Universities (No.10ykzd03).
文摘BRCA2,a clinical prognostic factor,is significantly up-regulated 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 BRCA23′-UTR and translation,impaired homologous recombination(HR)-mediated repair,reduced DNA damage-induced Rad51 nuclear foci,and rendered cells hypersensitive to g-irradiation(IR),ul-timately 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 up-regulated miR-1245 expression via direct binding to the miR-1245 promoter,which led to down-regulation of BRCA2 and reduction in 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.
文摘The immunohistochemistry(IHC)staining of MID2 in“ANT”from Patient 2 and“T”from Patient 6 in original Fig.2C(Page 45)should be corrected.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.
