| Literature DB >> 28777932 |
Joshua A Betts1, Mahdi Moradi Marjaneh2, Fares Al-Ejeh2, Yi Chieh Lim2, Wei Shi2, Haran Sivakumaran2, Romain Tropée3, Ann-Marie Patch2, Michael B Clark4, Nenad Bartonicek5, Adrian P Wiegmans2, Kristine M Hillman2, Susanne Kaufmann2, Amanda L Bain2, Brian S Gloss5, Joanna Crawford6, Stephen Kazakoff2, Shivangi Wani2, Shu W Wen2, Bryan Day2, Andreas Möller2, Nicole Cloonan2, John Pearson2, Melissa A Brown7, Timothy R Mercer5, Nicola Waddell2, Kum Kum Khanna2, Eloise Dray8, Marcel E Dinger5, Stacey L Edwards9, Juliet D French10.
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.Entities:
Keywords: 11q13; DNA repair; GWAS; breast cancer; enhancer; long noncoding RNAs
Mesh：
Substances：
Year: 2017 PMID： 28777932 PMCID： PMC5544418 DOI： 10.1016/j.ajhg.2017.07.007
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025