College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.
Department of Pathophysiology, School of Medicine, Southeast University, Nanjing, 210009, China.
Breast Cancer Res Treat. 2018 Jun;169(2):267-275. doi: 10.1007/s10549-018-4678-1. Epub 2018 Feb 1.
Breast cancer is one of the most common solid tumors in women involving multiple subtypes. However, the mechanism for subtypes of breast cancer is still complicated and unclear. Recently, several studies indicated that long non-coding RNAs (lncRNAs) could act as sponges to compete miRNAs with mRNAs, participating in various biological processes.
We concentrated on the competing interactions between lncRNAs and mRNAs in four subtypes of breast cancer (basal-like, HER2+, luminal A and luminal B), and analyzed the impacts of competing endogenous RNAs (ceRNAs) on each subtype systematically. We constructed four breast cancer subtype-related lncRNA-mRNA ceRNA networks by integrating the miRNA target information and the expression data of lncRNAs, miRNAs and mRNAs.
We constructed the ceRNA network for each breast cancer subtype. Functional analysis revealed that the subtype-related ceRNA networks were enriched in cancer-related pathways in KEGG, such as pathways in cancer, miRNAs in cancer, and PI3k-Akt signaling pathway. In addition, we found three common lncRNAs across the four subtype-related ceRNA networks, NEAT1, OPI5-AS1 and AC008124.1, which played specific roles in each subtype through competing with diverse mRNAs. Finally, the potential drugs for treatment of basal-like subtype could be predicted through reversing the differentially expressed lncRNA in the ceRNA network.
This study provided a novel perspective of lncRNA-involved ceRNA network to dissect the molecular mechanism for breast cancer.
乳腺癌是女性最常见的实体肿瘤之一,涉及多种亚型。然而,乳腺癌亚型的发生机制仍然复杂且不明确。最近,几项研究表明,长链非编码 RNA(lncRNA)可以作为 miRNA 的海绵体与 mRNAs 竞争,参与各种生物过程。
我们集中研究了四种乳腺癌亚型(基底样、HER2+、管腔 A 和管腔 B)中 lncRNA 和 mRNAs 之间的竞争相互作用,并系统分析了 ceRNA 对每种亚型的影响。我们通过整合 miRNA 靶标信息和 lncRNA、miRNA 和 mRNAs 的表达数据,构建了四个与乳腺癌亚型相关的 lncRNA-mRNA ceRNA 网络。
我们构建了每个乳腺癌亚型的 ceRNA 网络。功能分析表明,亚型相关的 ceRNA 网络在 KEGG 中富集了癌症相关途径,如癌症途径、癌症中的 miRNA 和 PI3k-Akt 信号通路。此外,我们发现了三个跨越四个亚型相关 ceRNA 网络的共有 lncRNA,包括 NEAT1、OPI5-AS1 和 AC008124.1,它们通过与不同的 mRNAs 竞争,在每个亚型中发挥特定作用。最后,可以通过逆转 ceRNA 网络中差异表达的 lncRNA 来预测治疗基底样亚型的潜在药物。
本研究提供了一种新的 lncRNA 参与 ceRNA 网络的视角,以剖析乳腺癌的分子机制。