<p>Construction of a circRNA-Related ceRNA Prognostic Regulatory Network in Breast Cancer</p>
作者：Huan Song, Jian Sun, Weimin Kong, Ye Ji, Dian Xu, Jianming Wang · 发表于：OncoTargets and Therapy · 年份：2020 · DOI：10.2147/ott.s266507 · 被引用次数：41 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、Cancer Mechanisms and Therapy
PURPOSE: Accumulating evidence has indicated that circRNAs are closely involved in tumorigenesis and progression of human cancers. However, the molecular mechanism underlying function of circRNAs in breast cancer has not been thoroughly elucidated. Currently, we aimed to characterize the circRNA-related competing endogenous RNA (ceRNA) regulatory network in breast cancer and to construct prognostic model. MATERIALS AND METHODS: First, we constructed circRNA expression profiles for paired breast cancer in a Chinese population using a human circRNA microarray. Expression profiles of circRNAs, miRNAs, and mRNAs were retrieved from our circRNA dataset, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We applied the limma and edgeR packages to identify differentially expressed RNAs. Weighted gene correlation network analysis (WGCNA) was used to identify critical modules of mRNAs. Next, a ceRNA network was established based on circRNA-miRNA and miRNA-mRNA intersections. Both Cox regression analysis and ROC curve analysis were performed to generate prognostic model. Additionally, we performed Gene Set Enrichment Analysis (GSEA) on prognostic signatures. RESULTS: Total of 59 circRNAs, 98 miRNAs and 3966 mRNAs were identified as differentially expressed RNAs. We first identified 38 miRNA-mRNA pairs and 38 circRNA-miRNA pairs to construct the circRNA-miRNA-mRNA regulatory network and then generated a prognostic model based on 7 signatures (MMD, SLC29A4, C...