College of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China 266000.
College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China 250000.
Biomed Res Int. 2020 Jul 24;2020:4078596. doi: 10.1155/2020/4078596. eCollection 2020.
Long noncoding RNAs (lncRNAs) act as competing endogenous RNAs for microRNAs in cancer metastasis. However, the roles of lncRNA-mediated competing endogenous RNA (ceRNA) networks for breast cancer (BC) are still unclear. . The expression profiles of mRNAs, lncRNAs, and miRNAs with BC were extracted from The Cancer Genome Atlas database. Weighted gene coexpression network analysis was conducted to extract differentially expressed mRNAs (DEmRNAs) that might be core genes. Through miRWalk, TargetScan, and miRDB to predict the target genes, an abnormal lncRNA-miRNA-mRNA ceRNA network with BC was constructed. The survival possibilities of mRNAs, miRNAs, and lncRNAs for patients with BC were determined by Kaplan-Meier survival curves and Oncomine.
We identified 2134 DEmRNAs, 1059 differentially expressed lncRNAs (DElncRNAs), and 86 differentially expressed miRNAs (DEmiRNAs). We then compose a ceRNA network for BC, including 72 DElncRNAs, 8 DEmiRNAs, and 12 DEmRNAs. After verification, 2 lncRNAs (LINC00466, LINC00460), 1 miRNA (Hsa-mir-204), and 5 mRNAs (TGFBR2, CDH2, CHRDL1, FGF2, and CHL1) were meaningful as prognostic biomarkers for BC patients. In the ceRNA network, we found that three axes were present in 10 RNAs related to the prognosis of BC, namely, LINC00466-Hsa-mir-204-TGFBR2, LINC00466-Hsa-mir-204-CDH2, and LINC00466-Hsa-mir-204-CHRDL1.
This study highlighted lncRNA-miRNA-mRNA ceRNA related to the pathogenesis of BC, which might be used for latent diagnostic biomarkers and therapeutic targets for BC.
长链非编码 RNA（lncRNA）在癌症转移中作为 microRNA 的竞争性内源 RNA（ceRNA）发挥作用。然而，lncRNA 介导的 ceRNA 网络在乳腺癌（BC）中的作用尚不清楚。本研究从癌症基因组图谱数据库中提取了与 BC 相关的 mRNA、lncRNA 和 miRNA 的表达谱。通过加权基因共表达网络分析提取可能是核心基因的差异表达 mRNA（DEmRNAs）。通过 miRWalk、TargetScan 和 miRDB 预测靶基因，构建了一个异常的 lncRNA-miRNA-mRNA ceRNA 网络。通过 Kaplan-Meier 生存曲线和 Oncomine 确定了 BC 患者的 mRNA、miRNA 和 lncRNA 的生存可能性。
我们鉴定出 2134 个 DEmRNAs、1059 个差异表达的 lncRNA（DElncRNAs）和 86 个差异表达的 miRNA（DEmiRNAs）。然后，我们构建了一个 BC 的 ceRNA 网络，包括 72 个 DElncRNAs、8 个 DEmiRNAs 和 12 个 DEmRNAs。经过验证，2 个 lncRNA（LINC00466、LINC00460）、1 个 miRNA（Hsa-mir-204）和 5 个 mRNA（TGFBR2、CDH2、CHRDL1、FGF2、CHL1）作为 BC 患者的预后生物标志物具有意义。在 ceRNA 网络中，我们发现与 BC 预后相关的 10 个 RNA 中有 3 个轴存在，即 LINC00466-Hsa-mir-204-TGFBR2、LINC00466-Hsa-mir-204-CDH2 和 LINC00466-Hsa-mir-204-CHRDL1。
本研究强调了与 BC 发病机制相关的 lncRNA-miRNA-mRNA ceRNA，可为 BC 的潜在诊断生物标志物和治疗靶点提供参考。
