Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer

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 upd...

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Main Authors: Mou Peng, Xu Cheng, Wei Xiong, Lu Yi, Yinhuai Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.684242/full
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spelling doaj-8cf15274d4324f21ba7c1a93db729af12021-08-02T14:29:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-08-011110.3389/fonc.2021.684242684242Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder CancerMou PengXu ChengWei XiongLu YiYinhuai WangLong 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.684242/fulllncRNA signatureceRNA networknomogramprognosisbladder cancer
collection DOAJ
language English
format Article
sources DOAJ
author Mou Peng
Xu Cheng
Wei Xiong
Lu Yi
Yinhuai Wang
spellingShingle Mou Peng
Xu Cheng
Wei Xiong
Lu Yi
Yinhuai Wang
Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer
Frontiers in Oncology
lncRNA signature
ceRNA network
nomogram
prognosis
bladder cancer
author_facet Mou Peng
Xu Cheng
Wei Xiong
Lu Yi
Yinhuai Wang
author_sort Mou Peng
title Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer
title_short Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer
title_full Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer
title_fullStr Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer
title_full_unstemmed Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer
title_sort integrated analysis of a competing endogenous rna network reveals a prognostic lncrna signature in bladder cancer
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2021-08-01
description 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.
topic lncRNA signature
ceRNA network
nomogram
prognosis
bladder cancer
url https://www.frontiersin.org/articles/10.3389/fonc.2021.684242/full
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