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, SMURF1, BTRC, and TP53, may further regulate tumorigenesis.

这项研究旨在鉴定新型环状RNA和相关的调控轴，为乳腺癌的诊断和治疗提供研究目标。从Gene Expression Omnibus数据库下载了与乳腺癌相关的环状RNA表达微阵列“ GSE101123”。使用Limma软件包筛选肿瘤与正常样品之间差异表达的环状RNA。分别使用miRanda和miRWalk预测了差异表达的环状RNA的靶向microRNA和微米RNA的信使RNA，并构建了环状RNA – microRNA – Messenger DNA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的构建以及药物-基因相互作用分析。在乳腺癌和正常样品之间共鉴定出11个差异表达的环状RNA，其中3个上调，而8个下调。环状RNA–microRNA–信使RNA网络包含1个环状RNA（hsa_circ_0000376），2个microRNA（miR-1285-3p和miR-1286）和353个信使RNA。蛋白质间相互作用网络包含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中枢基因都是miR-1285-3p的靶向信使RNA，在遍在蛋白-蛋白酶体系统，细胞凋亡，细胞周期阻滞相关的途径以及涉及SMAD特异性E3的与癌症相关的途径中均显着富集泛素蛋白连接酶1，β-转导重复序列，包含E3泛素蛋白连接酶，肿瘤蛋白P53等。预计有22种药物靶向4种信使RNA，包括肿瘤蛋白P53。在乳腺癌中发现了一种新型的环状RNA hsa_circ_0000376，它可以充当靶向miR-1285-3p表达的海绵，该海绵通过其靶基因，SMURF1，BTRC和TP53可能进一步调节肿瘤发生。