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

Am J Hum Genet.. 2017-08; 
Betts JA, Moradi Marjaneh M, Al-Ejeh F, Lim YC, Shi W, Sivakumaran H, Tropée R, Patch AM, Clark MB, Bartonicek N, Wiegmans AP, Hillman KM, Kaufmann S, Bain AL, Gloss BS, Crawford J, Kazakoff S, Wani S, Wen SW, Day B, Möller A, Cloonan N, Pearson J, Brown MA, Mercer TR, Waddell N, Khanna KK, Dray E, Dinger ME, Edwards SL, French JD.
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Gene Synthesis ... Sequences corresponding to the main isoforms of CUPID1 and CUPID2 ( Figure S2) were synthesized by GenScript and inserted into the Nhe1-Not1 or NheI-BamHI sites of pCDNA3.1. For re-establishment of CUPID1 and CUPID2 expression, the following procedures were ... Get A Quote

摘要

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 m... More

关键词

11q13; DNA repair; GWAS; breast cancer; enhancer; long noncoding RNAs