长链非编码RNA CUPID1和CUPID2通过调节对DNA损伤的反应介导11q13处的乳腺癌风险。
Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage.
作者信息
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, Möller Andreas, Cloonan Nicole, Pearson John, Brown Melissa A, Mercer Timothy R, Waddell Nicola, Khanna Kum Kum, Dray Eloise, Dinger Marcel E, Edwards Stacey L, French Juliet D
机构信息
Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
出版信息
Am J Hum Genet. 2017 Aug 3;101(2):255-266. doi: 10.1016/j.ajhg.2017.07.007.
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.
乳腺癌风险与11q13上的一个基因间区域密切相关。我们之前已经表明，最强的风险相关单核苷酸多态性（SNP）位于一个调控细胞周期蛋白D1（CCND1）的远端增强子内。在此，我们报告，除了调控CCND1外，这个增强子还调控两个雌激素调节的长链非编码RNA，即CUPID1和CUPID2。我们提供的证据表明，风险相关SNP与增强子和CUPID1及CUPID2双向启动子之间染色质环化减少有关。我们进一步表明，CUPID1和CUPID2主要在激素受体阳性的乳腺肿瘤中表达，并在调节双链断裂修复的途径选择中发挥作用。这些数据揭示了该区域参与乳腺癌发生的一种机制。
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