Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma

Background: Hepatitis C virus (HCV) infection contribute to liver fibrosis and cirrhosis, which significantly increases the risk of hepatocellular carcinoma (HCC) development. Previous studies have demonstrated the pivotal role of competitive endogenous RNA (ceRNA) networks in tumorigenesis and canc...

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Main Authors: Lishi Shao, Lei Liang, Qixiang Fang, Jiaping Wang
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240584402202120X
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author Lishi Shao
Lei Liang
Qixiang Fang
Jiaping Wang
author_facet Lishi Shao
Lei Liang
Qixiang Fang
Jiaping Wang
author_sort Lishi Shao
collection DOAJ
description Background: Hepatitis C virus (HCV) infection contribute to liver fibrosis and cirrhosis, which significantly increases the risk of hepatocellular carcinoma (HCC) development. Previous studies have demonstrated the pivotal role of competitive endogenous RNA (ceRNA) networks in tumorigenesis and cancer progression. Consequently, we herein seek to identify and evaluate the prognostic relevance of a novel ceRNA network associated with HCV-related HCC. Methods: Differentially expressed genes (DEGs) in GSE140846 dataset from GEO were identified using Network Analyst, and GO, KEGG and Reactome analyses were performed. Furthermore, a protein-protein interaction network was generated, and hub genes were detected. Hub gene expression levels, as well as those of their upstream lncRNAs and miRNAs and associated survival analyses were conducted using appropriate bioinformatics databases. Predicted target relationships were used to establish putative ceRNA networks for HCV-related HCC. Results: A total of 372 and 360 up- and down-regulated DE-mRNA were identified, which were associated with nuclear division, cell cycle, and ATPase activity. A PPI network containing 704 DE-mRNAs was constructed, and the 6 hub gene with the highest degree of connectivity were selected for subsequent analysis. We discovered that 22 miRNAs and 4 lncRNAs upstream of 11 hub gene were significantly associated with poor prognosis of HCV-related HCC, and used them to constructe a prognostic ceRNA network. Further experiments confirmed the ceRNA-regulatory relationship of BUB1-hsa-miR-193a-3p-MALAT1. Conclusion: This study provides novel insights into the lncRNA-miRNA-mRNA ceRNA network, and reveals potential lncRNA biomarkers in HCV related HCC.
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spelling doaj.art-30a7e1c0c6104acb9e51cf61a549dd682022-12-22T02:42:56ZengElsevierHeliyon2405-84402022-10-01810e10832Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinomaLishi Shao0Lei Liang1Qixiang Fang2Jiaping Wang3Department of Radiology, The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Avenue, Kunming, Yunnan 650101, PR ChinaDepartment of Oncology, The First Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, Yunnan 650032, PR ChinaDepartment of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, 277 Yanta Xi Lu, Xi 'an, Shaanxi 710061, PR ChinaDepartment of Radiology, The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Avenue, Kunming, Yunnan 650101, PR China; Corresponding author.Background: Hepatitis C virus (HCV) infection contribute to liver fibrosis and cirrhosis, which significantly increases the risk of hepatocellular carcinoma (HCC) development. Previous studies have demonstrated the pivotal role of competitive endogenous RNA (ceRNA) networks in tumorigenesis and cancer progression. Consequently, we herein seek to identify and evaluate the prognostic relevance of a novel ceRNA network associated with HCV-related HCC. Methods: Differentially expressed genes (DEGs) in GSE140846 dataset from GEO were identified using Network Analyst, and GO, KEGG and Reactome analyses were performed. Furthermore, a protein-protein interaction network was generated, and hub genes were detected. Hub gene expression levels, as well as those of their upstream lncRNAs and miRNAs and associated survival analyses were conducted using appropriate bioinformatics databases. Predicted target relationships were used to establish putative ceRNA networks for HCV-related HCC. Results: A total of 372 and 360 up- and down-regulated DE-mRNA were identified, which were associated with nuclear division, cell cycle, and ATPase activity. A PPI network containing 704 DE-mRNAs was constructed, and the 6 hub gene with the highest degree of connectivity were selected for subsequent analysis. We discovered that 22 miRNAs and 4 lncRNAs upstream of 11 hub gene were significantly associated with poor prognosis of HCV-related HCC, and used them to constructe a prognostic ceRNA network. Further experiments confirmed the ceRNA-regulatory relationship of BUB1-hsa-miR-193a-3p-MALAT1. Conclusion: This study provides novel insights into the lncRNA-miRNA-mRNA ceRNA network, and reveals potential lncRNA biomarkers in HCV related HCC.http://www.sciencedirect.com/science/article/pii/S240584402202120XHepatitis C virus Related hepatocellular carcinomaBioinformaticsPrognosisCompetitive endogenous RNANon-coding RNA
spellingShingle Lishi Shao
Lei Liang
Qixiang Fang
Jiaping Wang
Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma
Heliyon
Hepatitis C virus Related hepatocellular carcinoma
Bioinformatics
Prognosis
Competitive endogenous RNA
Non-coding RNA
title Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma
title_full Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma
title_fullStr Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma
title_full_unstemmed Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma
title_short Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma
title_sort construction of novel lncrna mirna mrna cerna networks associated with prognosis of hepatitis c virus related hepatocellular carcinoma
topic Hepatitis C virus Related hepatocellular carcinoma
Bioinformatics
Prognosis
Competitive endogenous RNA
Non-coding RNA
url http://www.sciencedirect.com/science/article/pii/S240584402202120X
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