Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820928471. doi: 10.1177/1533033820928471.
This study was designed to identify novel circular RNAs and the related regulatory axis to provide research targets for the diagnosis and treatment of breast cancer. The circular RNA expression microarray "GSE101123" related to breast cancer was downloaded from the Gene Expression Omnibus database. The differentially expressed circular RNAs between tumor and normal samples were screened using Limma package. The targeted microRNAs of the differentially expressed circular RNAs and the targeted messenger RNAs of the microRNAs were predicted using miRanda and miRWalk, respectively, and a circular RNAs-microRNAs-messenger RNAs network was constructed. Then, functional enrichment analysis, protein-protein interaction network construction, and drug-gene interaction analysis were conducted for the messenger RNAs. A total of 11 differentially expressed circular RNAs were identified between the breast cancer and normal samples, of which 3 were upregulated, while 8 were downregulated. The circular RNA-microRNA-messenger RNA network contained 1 circular RNA (hsa_circ_0000376), 2 microRNAs (miR-1285-3p and miR-1286), and 353 messenger RNAs. The protein-protein interaction network contained 150 nodes and 240 interactions. The hub genes in the protein-protein interaction network were all targeted messenger RNAs of miR-1285-3p that were significantly enriched in the ubiquitin-proteasome system, apoptosis, cell cycle arrest-related pathways, and cancer-related pathways involving SMAD specific E3 ubiquitin protein ligase 1, β-transducin repeat containing E3 ubiquitin protein ligase, tumor protein P53 among others. Twenty-two drugs were predicted to target 4 messenger RNAs, including tumor protein P53. A novel circular RNA, hsa_circ_0000376, was identified in breast cancer that may act as a sponge targeting miR-1285-3p expression which through its target genes, , and , may further regulate tumorigenesis.
本研究旨在鉴定新型环状 RNA 及其相关调控轴，为乳腺癌的诊断和治疗提供研究靶点。从基因表达综合数据库中下载与乳腺癌相关的环状 RNA 表达微阵列“GSE101123”。使用 Limma 包筛选肿瘤和正常样本之间差异表达的环状 RNA。使用 miRanda 和 miRWalk 分别预测差异表达环状 RNA 的靶向 microRNAs 和 microRNAs 的靶向信使 RNA，并构建环状 RNA-microRNAs-messenger RNA 网络。然后，对信使 RNA 进行功能富集分析、蛋白质-蛋白质相互作用网络构建和药物-基因相互作用分析。在乳腺癌和正常样本之间鉴定出 11 个差异表达的环状 RNA，其中 3 个上调，8 个下调。环状 RNA-microRNA-messenger RNA 网络包含 1 个环状 RNA（hsa_circ_0000376）、2 个 microRNAs（miR-1285-3p 和 miR-1286）和 353 个信使 RNA。蛋白质-蛋白质相互作用网络包含 150 个节点和 240 个相互作用。蛋白质-蛋白质相互作用网络中的枢纽基因都是 miR-1285-3p 的靶向信使 RNA，它们显著富集在泛素-蛋白酶体系统、细胞凋亡、细胞周期停滞相关途径以及涉及 SMAD 特异性 E3 泛素蛋白连接酶 1、β-转导素重复包含 E3 泛素蛋白连接酶、肿瘤蛋白 P53 等的癌症相关途径中。预测 22 种药物靶向 4 种信使 RNA，包括肿瘤蛋白 P53。在乳腺癌中鉴定出一种新型环状 RNA hsa_circ_0000376，它可能作为 miR-1285-3p 表达的海绵体，通过其靶基因 、 和 ，进一步调节肿瘤发生。
