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

Abstract

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.

Type Journal
ISBN 1537-6605 (Electronic) 0002-9297 (Linking)
Authors Betts, J. A.; Moradi Marjaneh, M.; Al-Ejeh, F.; Lim, Y. C.; Shi, W.; Sivakumaran, H.; Tropee, R.; Patch, A. M.; Clark, M. B.; Bartonicek, N.; Wiegmans, A. P.; Hillman, K. M.; Kaufmann, S.; Bain, A. L.; Gloss, B. S.; Crawford, J.; Kazakoff, S.; Wani, S.; Wen, S. W.; Day, B.; Moller, A.; Cloonan, N.; Pearson, J.; Brown, M. A.; Mercer, T. R.; Waddell, N.; Khanna, K. K.; Dray, E.; Dinger, M. E.; Edwards, S. L.; French, J. D.
Responsible Garvan Author (missing name)
Publisher Name AMERICAN JOURNAL OF HUMAN GENETICS
Published Date 2017-08-03
Published Volume 101
Published Issue 2
Published Pages 255-266
Status Published in-print
DOI 10.1016/j.ajhg.2017.07.007
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28777932