Peng Mou, Cheng Xu, Xiong Wei, Yi Lu, Wang Yinhuai
Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2021 Aug 2;11:684242. doi: 10.3389/fonc.2021.684242. eCollection 2021.
Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to regulate mRNA expression through sponging microRNA in tumorigenesis and progression. However, following the discovery of new RNA interaction, the differentially expressed RNAs and ceRNA regulatory network are required to update. Our study comprehensively analyzed the differentially expressed RNA and corresponding ceRNA network and thus constructed a potentially predictive tool for prognosis. "DESeq2" was used to perform differential expression analysis. Two hundred and six differentially expressed (DE) lncRNAs, 222 DE miRNAs, and 2,463 DE mRNAs were found in this study. The lncRNA-mRNA interactions in the miRcode database and the miRNA-mRNA interactions in the starBase, miRcode, and mirTarBase databases were searched, and a competing endogenous RNA (ceRNA) network with 186 nodes and 836 interactions was subsequently constructed. Aberrant expression patterns of lncRNA NR2F1-AS1 and lncRNA AC010168.2 were evaluated in two datasets (GSE89006, GSE31684), and real-time polymerase chain reaction was also performed to validate the expression pattern. Furthermore, we found that these two lncRNAs were independent prognostic biomarkers to generate a prognostic lncRNA signature by univariate and multivariate Cox analyses. According to the lncRNA signature, patients in the high-risk group were associated with a poor prognosis and validated by an external dataset. A novel genomic-clinicopathologic nomogram to improve prognosis prediction of bladder cancer was further plotted and calibrated. Our study deepens the understanding of the regulatory ceRNA network and provides an easy-to-do genomic-clinicopathological nomogram to predict the prognosis in patients with bladder cancer.
长链非编码RNA（lncRNAs）作为竞争性内源性RNA（ceRNAs），在肿瘤发生和进展过程中通过海绵吸附微小RNA来调节mRNA表达。然而，随着新的RNA相互作用的发现，差异表达的RNA和ceRNA调控网络需要更新。我们的研究全面分析了差异表达的RNA和相应的ceRNA网络，从而构建了一种潜在的预后预测工具。使用“DESeq2”进行差异表达分析。本研究发现了206个差异表达的（DE）lncRNAs、222个DE miRNAs和2463个DE mRNAs。搜索了miRcode数据库中的lncRNA-mRNA相互作用以及starBase、miRcode和mirTarBase数据库中的miRNA-mRNA相互作用，随后构建了一个具有186个节点和836个相互作用的竞争性内源性RNA（ceRNA）网络。在两个数据集（GSE89006、GSE31684）中评估了lncRNA NR2F1-AS1和lncRNA AC010168.2的异常表达模式，并进行了实时聚合酶链反应以验证表达模式。此外，我们发现这两个lncRNAs是独立的预后生物标志物，通过单变量和多变量Cox分析生成了一个预后lncRNA特征。根据lncRNA特征，高危组患者预后较差，并通过外部数据集进行了验证。进一步绘制并校准了一个新的基因组-临床病理列线图，以改善膀胱癌的预后预测。我们的研究加深了对ceRNA调控网络的理解，并提供了一个易于操作的基因组-临床病理列线图来预测膀胱癌患者的预后。
