Purpose. Circular RNA as a competitive endogenous RNA (ceRNA) plays a significant role in the pathogenesis and progression of breast cancer. In this study, a circular RNA-related ceRNA regulatory network was constructed, which provides new biomarkers and therapeutic targets for the treatment of breast cancer. Materials and methods. The expression profile datasets (GSE101123, GSE143564, GSE50428) of circRNAs, miRNAs, and mRNAs were downloaded from the GEO database, and then differentially expressed RNAs (DEcircRNAs, DEmiRNAs, DEmRNAs) were obtained through the CSCD, TargetScan, miRDB, and miRTarBase databases. CircRNA-miRNA pairs and miRNA-mRNA pairs were constructed. Finally, a ceRNA regulatory network was established. Downstream analysis of the ceRNA network included GO, KEGG analysis, survival analysis, sub-network construction, the BCIP, and qRT-PCR verification. Results. In total, 144 differentially expressed (DE) DEcircRNA, 221 DEmiRNA, and 1211 DEmRNA were obtained, and 96 circRNA-miRNA pairs and 139 miRNA-mRNA pairs were constructed by prediction. The ceRNA regulatory network (circRNA-miRNA-mRNA) was constructed, which included 42 circRNA, 36miRNA, and 78 mRNA. GO function annotation showed genes were mainly enriched in receptor activity activated by transforming growth factor beta (TGF-beta) and in the regulation of epithelial cell apoptosis. KEGG analysis showed genes were mainly enriched in the TGF-beta signaling, PI3K-Akt signaling, and Wnt signaling pathways. Four genes associated with survival and prognosis of breast cancer were obtained by survival analysis, the prognostic sub-network included 4 circRNA, 4 miRNA, and 4 mRNA. BCIP analysis and qRT-PCR verification confirmed that relative mRNA expression levels were consistent with those in the GEO database. Conclusion. A circRNA-related ceRNA regulatory network was constructed for breast cancer in this study and key genes affecting pathogenesis and progression were identified. These findings may help better understand and further explore the molecular mechanisms that affect the progression and pathogenesis of breast cancer.

中文翻译：

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竞争性内源性RNA调控网络的筛选和生物信息学分析——与乳腺癌中的环状RNA相关

目的。环状RNA作为一种竞争性内源性RNA（ceRNA）在乳腺癌的发病机制和进展中发挥着重要作用。本研究构建了环状RNA相关的ceRNA调控网络，为乳腺癌的治疗提供了新的生物标志物和治疗靶点。材料和方法. 从GEO数据库下载circRNAs、miRNAs和mRNAs的表达谱数据集（GSE101123、GSE143564、GSE50428），然后通过CSCD、TargetScan、miRDB和miRtarBase数据库获得差异表达的RNAs（DEcircRNAs、DEmiRNAs、DEmRNAs） . 构建了CircRNA-miRNA对和miRNA-mRNA对。最后，建立了ceRNA监管网络。ceRNA网络的下游分析包括GO、KEGG分析、生存分析、子网络构建、BCIP和qRT-PCR验证。结果. 总共获得了144个差异表达（DE）的DEcircRNA、221个DEmiRNA和1211个DEmRNA，通过预测构建了96个circRNA-miRNA对和139个miRNA-mRNA对。构建了ceRNA调控网络（circRNA-miRNA-mRNA），包括42个circRNA、36个miRNA和78个mRNA。GO功能注释显示基因主要富集于由转化生长因子β（TGF-β）激活的受体活性和上皮细胞凋亡的调节中。KEGG 分析显示基因主要富集在 TGF-beta 信号通路、PI3K-Akt 信号通路和 Wnt 信号通路中。通过生存分析得到4个与乳腺癌生存和预后相关的基因，预后子网络包括4个circRNA、4个miRNA和4个mRNA。结论。本研究为乳腺癌构建了一个与circRNA相关的ceRNA调控网络，并确定了影响发病和进展的关键基因。这些发现可能有助于更好地理解和进一步探索影响乳腺癌进展和发病机制的分子机制。