QIMR Berghofer

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage


Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

Authors Betts, Joshua A.; Marjaneh, Mahdi Moradi; Al-Ejeh, Fares; Lim, Yi Chieh; Shi, Wei; Sivakumaran, Haran; Tropee, Romain; Patch, Ann-Marie; Clark, Michael B.; Bartonicek, Nenad; Wiegmans, Adrian P.; Hillman, Kristine M.; Kaufmann, Susanne; Bain, Amanda L.; Gloss, Brian S.; Crawford, Joanna; Kazakoff, Stephen; Wani, Shivangi; Wen, Shu W.; Day, Bryan; Moller, Andreas; Cloonan, Nicole; Pearson, John; Brown, Melissa A.; Mercer, Timothy R.; Waddell, Nicola; Khanna, Kum Kum; Dray, Eloise; Dinger, Marcel E.; Edwards, Stacey L.; French, Juliet D.
Pages 255-266
Volume 101
Date 1/08/2017
Grant ID 1021731
Funding Body National Health and Medical Research Council of Australia (NHMRC)
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.ajhg.2017.07.007