MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours.

MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours.
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DOI:
10.1186/s12885-017-3751-1
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发表时间:
2017-11-07
期刊:
影响因子:
3.8
通讯作者:
Krol M
Krol M
中科院分区:
医学2区
文献类型:
--
作者:
Bulkowska M;Rybicka A;Senses KM;Ulewicz K;Witt K;Szymanska J;Taciak B;Klopfleisch R;Hellmén E;Dolka I;Gure AO;Mucha J;Mikow M;Gizinski S;Krol M

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MicroRNA可能作为癌基因或肿瘤抑制基因,这使得这些小分子成为潜在的诊断/预后因子和抗癌治疗的靶点。在犬乳腺癌和人乳腺癌中发现了几种常见的致癌microRNA。因此,犬乳腺癌中microRNA表达的大规模分析似乎对犬和人类都很重要。对146例不同组织学类型、恶性程度和临床病史(有/无转移)的犬乳腺肿瘤和25例对照样本中317种microRNA的表达谱进行了评价。使用微阵列进行分析。微阵列数据的分析采用微阵列显著性分析检验(进行无监督和监督数据分析)。使用实时qPCR对所得结果进行验证。随后,在miRBase中搜索microRNA的预测靶标。非监督分析的结果表明,分离样本的主要因素是转移状态。在转移性与非转移性组中差异表达的microRNA的预测靶标主要参与细胞周期调节、细胞分化和DNA损伤修复。另一方面,监督分析揭示了肿瘤类型、恶性程度和转移因子特有的差异表达的microRNA簇。在转移组和非转移组之间观察到microRNA表达的最显著差异,这表明microRNA在转移过程中的作用比在恶性转化中更重要。此外,差异表达的微小RNA构成了潜在的转移标志物。然而,血液样本中cfa-miR-144、cfa-miR-32和cfa-miR-374 a水平的验证并未遵循在非转移性和转移性肿瘤中观察到的变化。本文的在线版本(10.1186/s12885-017-3751-1)包含补充材料,可供授权用户使用。
MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans. Expression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases) and in 25 control samples were evaluated. The profiling was performed using microarrays. Significance Analysis of Microarrays test was applied in the analysis of microarray data (both unsupervised and supervised data analyses were performed). Validation of the obtained results was performed using real-time qPCR. Subsequently, predicted targets for the microRNAs were searched for in miRBase. Results of the unsupervised analysis indicate that the primary factor separating the samples is the metastasis status. Predicted targets for microRNAs differentially expressed in the metastatic vs. non-metastatic group are mostly engaged in cell cycle regulation, cell differentiation and DNA-damage repair. On the other hand, the supervised analysis reveals clusters of differentially expressed microRNAs unique for the tumour type, malignancy grade and metastasis factor. The most significant difference in microRNA expression was observed between the metastatic and non-metastatic group, which suggests a more important role of microRNAs in the metastasis process than in the malignant transformation. Moreover, the differentially expressed microRNAs constitute potential metastasis markers. However, validation of cfa-miR-144, cfa-miR-32 and cfa-miR-374a levels in blood samples did not follow changes observed in the non-metastatic and metastatic tumours. The online version of this article (10.1186/s12885-017-3751-1) contains supplementary material, which is available to authorized users.
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