학술논문
Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage.
Document Type
Article
Author
Betts, Joshua A.; Moradi Marjaneh, Mahdi; Al-Ejeh, Fares; Lim, Yi Chieh; Shi, Wei; Sivakumaran, Haran; Tropée, 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
Source
Subject
*BREAST cancer
*NON-coding RNA
*DNA repair
*GENE enhancers
*CHROMATIN
*SINGLE nucleotide polymorphisms
*
*
*
*
*
Language
ISSN
0002-9297
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. [ABSTRACT FROM AUTHOR]