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携带和不携带种系BRCA突变的乳腺癌患者中let-7a和miR-335的表达状态。

Expression status of let-7a and miR-335 among breast tumors in patients with and without germ-line BRCA mutations.

作者信息

Erturk Elif, Cecener Gulsah, Egeli Unal, Tunca Berrin, Tezcan Gulcin, Gokgoz Sehsuvar, Tolunay Sahsine, Tasdelen Ismet

机构信息

Department of Medical Biology, Institute of Health Sciences, Uludag University, Bursa, Turkey.

出版信息

Mol Cell Biochem. 2014 Oct;395(1-2):77-88. doi: 10.1007/s11010-014-2113-4. Epub 2014 Jun 19.

Abstract

The genetic factors of cancer predisposition remain elusive in the majority of familial and/or early-onset cases of breast cancer (BC). This type of BC is promoted by germ-line mutations that inactivate BRCA1 or BRCA2. On the other hand, recent studies have indicated that alterations in the levels of miRNA expression are linked to this disease. Although BRCA1 and BRCA2 gene mutations have been reported to commonly lead to alterations in genes that encode cancer-related proteins, little is known regarding the putative impact of these mutations on noncoding miRNAs. In the present study, we aimed to determine whether miRNA dysregulation is involved in the pathogenesis of BRCA-mutated BC. An expression analysis of 14 human miRNAs previously shown to be related to BC diagnosis, prognosis, and drug resistance was conducted using tissues from 60 familial and/or early-onset patients whose peripheral blood samples had been screened for BRCA1 and BRCA2 mutations through sequence analysis. Let-7a and miR-335 expression levels were significantly downregulated in the tumors of patients with a BRCA mutation compared with those of patients without a BRCA mutation (P = 0.04 and P = 0.02, respectively). Our results defined the associations between the expression status of let-7a and miR-335 and BRCA mutations. The expression analysis of these miRNAs might be used as biomarkers of the BRCA mutation status of early-onset and/or familial BC.

摘要

在大多数家族性和/或早发性乳腺癌(BC)病例中,癌症易感性的遗传因素仍不清楚。这种类型的乳腺癌是由使BRCA1或BRCA2失活的种系突变所引发的。另一方面,最近的研究表明,miRNA表达水平的改变与这种疾病有关。虽然据报道BRCA1和BRCA2基因突变通常会导致编码癌症相关蛋白的基因发生改变,但对于这些突变对非编码miRNA的假定影响却知之甚少。在本研究中,我们旨在确定miRNA失调是否参与BRCA突变型乳腺癌的发病机制。使用来自60例家族性和/或早发性患者的组织进行了14种先前已证明与乳腺癌诊断、预后和耐药性相关的人类miRNA的表达分析,这些患者的外周血样本已通过序列分析筛查BRCA1和BRCA2突变。与无BRCA突变的患者相比,BRCA突变患者肿瘤中的Let-7a和miR-335表达水平显著下调(分别为P = 0.04和P = 0.02)。我们的结果确定了let-7a和miR-335的表达状态与BRCA突变之间的关联。这些miRNA的表达分析可能用作早发性和/或家族性乳腺癌BRCA突变状态的生物标志物。

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