Network analysis of EMT and MET micro-RNA regulation in breast cancer.

Network analysis of EMT and MET micro-RNA regulation in breast cancer.
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DOI:
10.1038/s41598-017-13903-1
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发表时间:
2017-10-19
期刊:
影响因子:
4.6
通讯作者:
Hernández-Lemus E
Hernández-Lemus E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Drago-García D;Espinal-Enríquez J;Hernández-Lemus E

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在过去的几年中,microRNAs(miRs)已被证明对乳腺肿瘤的建立和发展至关重要。为了了解miR在乳腺癌中对转录调控的影响,我们构建了86个TCGA匹配的乳腺浸润性癌和对照组织RNA-Seq和miRNA-Seq测序数据的互信息网络。我们表明,miR是肿瘤和控制数据网络结构的决定因素。在肿瘤数据网络中,miR-200、miR-199和邻近的miR似乎通过生物学过程:上皮-间充质转化(EMT)和间充质向上皮转化(MET)在上皮和间充质性状的获得的调节上合作。尽管肿瘤和对照网络之间存在结构差异,但我们发现miR-200家族成员与Vim,ZEB-1/2和TWIST-1/2等基因之间存在保守的关联。此外,在肿瘤网络中观察到的大量miR映射到DLK 1-DIO 3(Chr 14 q32)中的特定染色体位置;这些miR中的一些也与EMT和MET调节相关。与EMT和TGF-β相关的通路加强了miR-200、miR-199和DLK 1-DIO 3簇在乳腺癌中的相关性。通过这种方法,我们强调,miR纳入基因调控网络的建设,提高了我们对乳腺癌生物学基础的调控机制的理解。
Over the last years, microRNAs (miRs) have shown to be crucial for breast tumour establishment and progression. To understand the influence that miRs have over transcriptional regulation in breast cancer, we constructed mutual information networks from 86 TCGA matched breast invasive carcinoma and control tissue RNA-Seq and miRNA-Seq sequencing data. We show that miRs are determinant for tumour and control data network structure. In tumour data network, miR-200, miR-199 and neighbour miRs seem to cooperate on the regulation of the acquisition of epithelial and mesenchymal traits by the biological processes: Epithelial-Mesenchymal Transition (EMT) and Mesenchymal to Epithelial Transition (MET). Despite structural differences between tumour and control networks, we found a conserved set of associations between miR-200 family members and genes such as VIM, ZEB-1/2 and TWIST-1/2. Further, a large number of miRs observed in tumour network mapped to a specific chromosomal location in DLK1-DIO3 (Chr14q32); some of those miRs have also been associated with EMT and MET regulation. Pathways related to EMT and TGF-beta reinforce the relevance of miR-200, miR-199 and DLK1-DIO3 cluster in breast cancer. With this approach, we stress that miR inclusion in gene regulatory network construction improves our understanding of the regulatory mechanisms underlying breast cancer biology.
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