Journal article

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

Joshua A Betts, Mahdi Moradi Marjaneh, Fares Al-Ejeh, Yi Chieh Lim, Wei Shi, Haran Sivakumaran, Romain Tropee, Ann-Marie Patch, Michael B Clark, Nenad Bartonicek, Adrian P Wiegmans, Kristine M Hillman, Susanne Kaufmann, Amanda L Bain, Brian S Gloss, Joanna Crawford, Stephen Kazakoff, Shivangi Wani, Shu W Wen, Bryan Day Show all



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. T..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Australian Research Council

Awarded by NHMRC

Awarded by EMBO

Awarded by National Breast Cancer Foundation

Funding Acknowledgements

This work was supported by grants (1021731 and 1058421) from the National Health and Medical Research Council of Australia (NHMRC). J.D.F., S.L.E., and A.P.W. were supported by fellowships from the Australian National Breast Cancer Foundation, J.A.B. was supported by an Australian postgraduate scholarship, F.A.-E. was supported by a Future Fellowship from the Australian Research Council (FT130101417), M.B.C. was supported by an NHMRC Early Career Fellowship (APP1072662) and EMBO Long-Term Fellowship (ALTF 864-2013), N.W. was supported by an NHMRC Career Development Fellowship (APP1112113), and K.K.K. was supported by an NHMRC Senior Principal Research Fellowship. The results published in this study are in part based on data generated by The Cancer Genome Atlas Research Network. The contents of the published material are solely the responsibility of the administering institution, a participating institution, or individual authors and do not reflect the views of the NHMRC.