Research Papers:

Competing endogenous RNA network analysis identifies critical genes among the different breast cancer subtypes

Juan Chen, Juan Xu, Yongsheng Li, Jinwen Zhang, Hong Chen, Jianping Lu, Zishan Wang, Xueying Zhao, Kang Xu, Yixue Li, Xia Li and Yan Zhang _

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Oncotarget. 2017; 8:10171-10184. https://doi.org/10.18632/oncotarget.14361

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Juan Chen1,*, Juan Xu1,*, Yongsheng Li1,*, Jinwen Zhang1, Hong Chen1, Jianping Lu1, Zishan Wang1, Xueying Zhao1, Kang Xu1, Yixue Li1, Xia Li1, Yan Zhang1

1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

*These authors have contributed equally to this work

Correspondence to:

Yan Zhang, email: tyozhang@ems.hrbmu.edu.cn

Xia Li, email: lixia@hrbmu.edu.cn

Yixue Li, email: yxli@sibs.ac.cn

Keywords: breast cancer, subtypes, miRNA, competing endogenous RNAs, network hubs

Received: September 30, 2016     Accepted: December 15, 2016     Published: December 29, 2016


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.

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