Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.
Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.
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DOI：
10.1002/emmm.201100136
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发表时间：
2011-05
影响因子：
11.1
通讯作者：
Mazoyer, Sylvie
中科院分区：
文献类型：
--
作者：
Garcia, Amandine I.;Buisson, Monique;Bertrand, Pascale;Rimokh, Ruth;Rouleau, Etienne;Lopez, Bernard S.;Lidereau, Rosette;Mikaelian, Ivan;Mazoyer, Sylvie
BRCA1基因的种系突变使女性易患乳腺癌（终生风险高达80%）。此外，在大约三分之一的散发性乳腺癌中，BRCA1蛋白缺失或含量极低。然而，BRCA1体细胞失活的机制似乎是多种多样的，仍然没有完全理解。我们在这里报道了miR-146a和miR-146b-5p的参与，它们结合在BRCA1的3'UTR的同一位点上，并通过报告基因试验下调其表达。通过转染乳腺细胞系中的microRNA （miRNA）前体或抑制剂，内源性BRCA1基因进一步证实了这一点。这种下调伴随着增殖增加和同源重组率降低，这两个过程由BRCA1控制。此外，我们发现在基底样乳腺肿瘤上皮细胞系和三阴性乳腺肿瘤中发现了最高水平的miR-146a和/或miR-146b-5p，这与BRCA1突变携带者产生的肿瘤最接近。这项工作为mirna通过下调BRCA1参与散发性乳腺癌提供了进一步证据。
Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still not fully understood. We report here the involvement of miR-146a and miR-146b-5p that bind to the same site in the 3′UTR of BRCA1 and down-regulate its expression as demonstrated using reporter assays. This was further confirmed with the endogenous BRCA1 gene by transfecting microRNA (miRNA) precursors or inhibitors in mammary cell lines. This down-regulation was accompanied by an increased proliferation and a reduced homologous recombination rate, two processes controlled by BRCA1. Furthermore, we showed that the highest levels of miR-146a and/or miR-146b-5p are found in basal-like mammary tumour epithelial cell lines and in triple negative breast tumours, which are the closest to tumours arising in carriers of BRCA1 mutations. This work provides further evidence for the involvement of miRNAs in sporadic breast cancer through down-regulation of BRCA1.
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DOI：
10.1073/pnas.98.1.130
发表时间：
2001-01-02
影响因子：
11.1
作者：
Beger, C;Pierce, LN;Wong-Staal, F
通讯作者：
Wong-Staal, F
影响因子：
11.2
作者：
Hurst DR;Edmonds MD;Scott GK;Benz CC;Vaidya KS;Welch DR
通讯作者：
Welch DR
影响因子：
5.3
作者：
Baldassarre, G;Battista, S;Fusco, A
通讯作者：
Fusco, A
影响因子：
11.5
作者：
Lakhani, SR;Manek, S;Easton, DF
通讯作者：
Easton, DF
影响因子：
10.3
作者：
Esteller, M;Silva, JM;Herman, JG
通讯作者：
Herman, JG