Breast cancer is a heterogeneous disease highly diverse in different subtypes, including hormone receptor positive and hormone receptor negative subtypes with variable malignancy, therapy regimen, and different prognosis. In this study, we develop a hormone receptor-specific mRNA–miRNA–lncRNA ceRNA network to identify whether several RNAs play fundamental roles in development and metastasis of breast cancer. To understand the association of ceRNA expression profiles in different breast cancer subgroups, the expression profiles and clinical information of 428 HR+/Her-2− breast cancer samples and 113 triple negative breast cancer samples were downloaded from The Cancer Genome Atlas database (TCGA). We comprehensively integrated and compared expression profiles of mRNAs, miRNAs, and lncRNAs between the two subgroups mentioned. Aberrantly expressed hormone receptor specific RNAs were identified, whereas lncRNA–miRNA interactions predicted by miRcode and miRNA-targeted mRNA interactions were validated by miRTarBase, Targetscan, and miRDB database. In this study, mRNA–miRNA–lncRNA ceRNA network was constructed that consisted of 44 miRNA–lncRNA interaction pairs and 2 miRNA–mRNA interaction pairs, and visualized by Cytoscape software. Prognostic markers of HR-specific subtype of breast cancer associated with overall survival were identified by Kaplan–Meier survival analysis. Finally, SFRP1, AC006449.1, and MUC2 were novel clinical predictors that may also provide a new therapeutic target in the future.

中文翻译：

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mRNA-miRNA-lncRNA ceRNA 网络在人类 HR+/Her-2- 乳腺癌和三阴性乳腺癌中的综合分析。

乳腺癌是一种异质性疾病，在不同亚型中高度多样化，包括激素受体阳性和激素受体阴性亚型，具有不同的恶性程度、治疗方案和不同的预后。在这项研究中，我们开发了一个激素受体特异性 mRNA-miRNA-lncRNA ceRNA 网络，以确定几种 RNA 是否在乳腺癌的发展和转移中起重要作用。为了了解不同乳腺癌亚组中 ceRNA 表达谱的关联，从癌症基因组图谱数据库 (TCGA) 下载了 428 个 HR+/Her-2− 乳腺癌样本和 113 个三阴性乳腺癌样本的表达谱和临床信息。我们综合整合并比较了上述两个亚组之间 mRNA、miRNA 和 lncRNA 的表达谱。鉴定了异常表达的激素受体特异性 RNA，而 miRcode 预测的 lncRNA-miRNA 相互作用和 miRNA 靶向 mRNA 相互作用由 miRTarBase、Targetscan 和 miRDB 数据库验证。在本研究中，构建了由 44 个 miRNA-lncRNA 相互作用对和 2 个 miRNA-mRNA 相互作用对组成的 mRNA-miRNA-lncRNA ceRNA 网络，并通过 Cytoscape 软件进行可视化。通过 Kaplan-Meier 生存分析确定了与总生存相关的乳腺癌 HR 特异性亚型的预后标志物。最后，SFRP1、AC006449.1 和 MUC2 是新的临床预测因子，也可能在未来提供新的治疗靶点。Targetscan 和 miRDB 数据库。在本研究中，构建了由 44 个 miRNA-lncRNA 相互作用对和 2 个 miRNA-mRNA 相互作用对组成的 mRNA-miRNA-lncRNA ceRNA 网络，并通过 Cytoscape 软件进行可视化。通过 Kaplan-Meier 生存分析确定了与总生存相关的乳腺癌 HR 特异性亚型的预后标志物。最后，SFRP1、AC006449.1 和 MUC2 是新的临床预测因子，也可能在未来提供新的治疗靶点。Targetscan 和 miRDB 数据库。在本研究中，构建了由 44 个 miRNA-lncRNA 相互作用对和 2 个 miRNA-mRNA 相互作用对组成的 mRNA-miRNA-lncRNA ceRNA 网络，并通过 Cytoscape 软件进行可视化。通过 Kaplan-Meier 生存分析确定了与总生存相关的乳腺癌 HR 特异性亚型的预后标志物。最后，SFRP1、AC006449.1 和 MUC2 是新的临床预测因子，也可能在未来提供新的治疗靶点。