Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma

Background/Aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we...

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Main Authors: Zhiyuan Zhang, Wenwei Qian, Sen Wang, Dongjian Ji, Qingyuan Wang, Jie Li, Wen Peng, Jiou Gu, Tao Hu, Bing Ji, Yue Zhang, Shijia Wang, Yueming Sun
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-09-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/493623
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author Zhiyuan Zhang
Wenwei Qian
Sen Wang
Dongjian Ji
Qingyuan Wang
Jie Li
Wen Peng
Jiou Gu
Tao Hu
Bing Ji
Yue Zhang
Shijia Wang
Yueming Sun
author_facet Zhiyuan Zhang
Wenwei Qian
Sen Wang
Dongjian Ji
Qingyuan Wang
Jie Li
Wen Peng
Jiou Gu
Tao Hu
Bing Ji
Yue Zhang
Shijia Wang
Yueming Sun
author_sort Zhiyuan Zhang
collection DOAJ
description Background/Aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD. Methods: We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR). Results: Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log2 [fold change] > 2, false discovery rate < 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR. Conclusion: This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.
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spelling doaj.art-daa81445f9574485b10744076653ec472022-12-22T00:21:49ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-09-014951778179110.1159/000493623493623Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon AdenocarcinomaZhiyuan ZhangWenwei QianSen WangDongjian JiQingyuan WangJie LiWen PengJiou GuTao HuBing JiYue ZhangShijia WangYueming SunBackground/Aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD. Methods: We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR). Results: Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log2 [fold change] > 2, false discovery rate < 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR. Conclusion: This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.https://www.karger.com/Article/FullText/493623Colon adenocarcinomaLncRNAceRNA networkBiomarkersBioinformatics analysis
spellingShingle Zhiyuan Zhang
Wenwei Qian
Sen Wang
Dongjian Ji
Qingyuan Wang
Jie Li
Wen Peng
Jiou Gu
Tao Hu
Bing Ji
Yue Zhang
Shijia Wang
Yueming Sun
Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma
Cellular Physiology and Biochemistry
Colon adenocarcinoma
LncRNA
ceRNA network
Biomarkers
Bioinformatics analysis
title Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma
title_full Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma
title_fullStr Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma
title_full_unstemmed Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma
title_short Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma
title_sort analysis of lncrna associated cerna network reveals potential lncrna biomarkers in human colon adenocarcinoma
topic Colon adenocarcinoma
LncRNA
ceRNA network
Biomarkers
Bioinformatics analysis
url https://www.karger.com/Article/FullText/493623
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