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首页> 外文期刊>BMC Cancer >miRNA expression profiling of hereditary breast tumors from BRCA1- and BRCA2-germline mutation carriers in Brazil
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miRNA expression profiling of hereditary breast tumors from BRCA1- and BRCA2-germline mutation carriers in Brazil

机译：巴西BRCA1和BRCA2-GRCA2-GRCA2-GRCA2-GRCA2-GRCA2-GRCA2-GRCA2-GRCAL的miRNA表达探讨

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BackgroundMicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis. Aberrant miRNA expression has been frequently reported in sporadic breast cancers, but few studies have focused on profiling hereditary breast cancers. In this study, we aimed to identify specific miRNA signatures in hereditary breast tumors and to compare with sporadic breast cancer and normal breast tissues.MethodsGlobal miRNA expression profiling using NanoString technology was performed on 43 hereditary breast tumors (15 BRCA1, 14 BRCA2, and 14 BRCAX), 23 sporadic breast tumors and 8 normal breast tissues. These normal breast tissues derived from BRCA1 - and BRCA2 - mutation carriers ( n =?5) and non-mutation carriers ( n =?3). Subsequently, we performed receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performance of differentially expressed miRNAs. Putative target genes of each miRNAs considered as potential biomarkers were identified using miRDIP platform and used for pathway enrichment analysis.ResultsmiRNA expression analyses identified several profiles that were specific to hereditary breast cancers. A total of 25 miRNAs were found to be differentially expressed (fold change: ?2.0 and p ?0.05) and considered as potential biomarkers (area under the curve ?0.75) in hereditary breast tumors compared to normal breast tissues, with an expressive upregulation among BRCAX cases. Furthermore, bioinformatic analysis revealed that these miRNAs shared target genes involved in ErbB, FoxO, and PI3K-Akt signaling pathways.ConclusionsOur results showed that miRNA expression profiling can differentiate hereditary from sporadic breast tumors and normal breast tissues. These miRNAs were remarkably deregulated in BRCAX hereditary breast cancers. Therefore, miRNA signatures can be used as potential novel diagnostic biomarkers for the prediction of BRCA1/2 - germline mutations and may be useful for future clinical management.
机译：背景模糊（MiRNA）是涉及转录后基因表达调节的小非编码RNA，并且已被描述为致癌物的关键调节剂。异常miRNA表达已经在散发性乳腺癌中经常报道，但很少有研究专注于分析遗传性乳腺癌。在这项研究中，我们旨在鉴定遗传性乳腺肿瘤中的特异性miRNA签名，并与散发性乳腺癌和正常乳腺组织进行比较。在43个遗传性乳腺肿瘤（15 brca1,14 brca2和14 Brcax），23次散发性乳腺肿瘤和8个正常乳腺组织。这些正常乳腺组织衍生自BRCA1 - 和BRCA2 - 突变载体（n =Δ5）和非突变载体（n =Δ3）。随后，我们执行了接收器操作特征（ROC）曲线分析以评估差异表达MIRNA的诊断性能。使用MiRdip平台鉴定了被认为是潜在的生物标志物的每个miRNA的推定靶基因，并用于途径富集分析。鉴定分析分析，鉴定了几种特异于遗传性乳腺癌的曲线。发现总共25个miRNA被差异表达（折叠变化：>？2.0和P <0.05），并被认为是遗传性乳腺肿瘤中的潜在生物标志物（曲线下的区域> 0.75），与正常乳腺组织相比，有一个BRCAX案件中的表达上调。此外，生物信息分析表明，这些miRNA共享靶基因涉及erbB，Foxo和Pi3k-akt信号传导途径。结合结果表明，MiRNA表达分析可以区分血管乳腺肿瘤和正常乳腺组织的遗传性。这些miRNA在Brcax遗传性乳腺癌中非常注释。因此，MiRNA签名可用作潜在的新型诊断生物标志物，用于预测BRCA1 / 2 - 种系突变，可用于未来的临床管理。

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