Chen Juan, Xu Juan, Li Yongsheng, Zhang Jinwen, Chen Hong, Lu Jianping, Wang Zishan, Zhao Xueying, Xu Kang, Li Yixue, Li Xia, Zhang Yan
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Oncotarget. 2017 Feb 7;8(6):10171-10184. doi: 10.18632/oncotarget.14361.
Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks. Furthermore, the common ceRNA hubs had greater connectivity than the subtype-specific hubs. Functional analysis of the common subtype ceRNA hubs highlighted factors involved in proliferation, MAPK signaling pathways and tube morphogenesis. Subtype-specific ceRNA hubs highlighted unique subtype-specific pathways, like the estrogen response and inflammatory pathways in the luminal subtypes or the factors involved in the coagulation process that participates in the basal-like subtype. Ultimately, we identified 29 critical subtype-specific ceRNA hubs that characterized the different breast cancer subtypes. Our study thus provides new insight into the common and specific subtype ceRNA interactions that define the different categories of breast cancer and enhances our understanding of the pathology underlying the different breast cancer subtypes, which can have prognostic and therapeutic implications in the future.
尽管竞争性内源性RNA（ceRNA）已被证明与多种实体瘤有关，但其在乳腺癌亚型中的作用仍未完全明确。因此，我们基于相应亚型miRNA失调网络中正向共表达和共享miRNA的重要性，为每个亚型构建了一个ceRNA网络，该miRNA失调网络是基于差异表达的miRNA与其靶标之间的负调控构建的。所有四个亚型的ceRNA网络均呈现无标度结构，且表明常见的ceRNA位于网络核心。此外，常见的ceRNA枢纽比亚型特异性枢纽具有更高的连接性。对常见亚型ceRNA枢纽的功能分析突出了参与增殖、MAPK信号通路和管形态发生的因子。亚型特异性ceRNA枢纽突出了独特的亚型特异性通路，如腔面亚型中的雌激素反应和炎症通路，或参与基底样亚型凝血过程的因子。最终，我们鉴定出29个关键的亚型特异性ceRNA枢纽，它们可区分不同的乳腺癌亚型。我们的研究因此为定义不同类别乳腺癌的常见和特定亚型ceRNA相互作用提供了新见解，并加深了我们对不同乳腺癌亚型病理基础的理解，这可能在未来具有预后和治疗意义。
