Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma

Abstract Background Hodgkin Lymphoma (HL) is a type of aggressive malignancy in lymphoma that has high incidence in young adults and elderly patients. Identification of reliable diagnostic markers and efficient therapeutic targets are especially important for the diagnosis and treatment of HL. Altho...

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Main Authors: Huimin Lei, Wenxu Liu, Jiarui Si, Ju Wang, Tao Zhang
Format: Article
Language:English
Published: BMC 2019-09-01
Series:BMC Bioinformatics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12859-019-3041-9
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author Huimin Lei
Wenxu Liu
Jiarui Si
Ju Wang
Tao Zhang
author_facet Huimin Lei
Wenxu Liu
Jiarui Si
Ju Wang
Tao Zhang
author_sort Huimin Lei
collection DOAJ
description Abstract Background Hodgkin Lymphoma (HL) is a type of aggressive malignancy in lymphoma that has high incidence in young adults and elderly patients. Identification of reliable diagnostic markers and efficient therapeutic targets are especially important for the diagnosis and treatment of HL. Although many HL-related molecules have been identified, our understanding on the molecular mechanisms underlying the disease is still far from complete due to its complex and heterogeneous characteristics. In such situation, exploring the molecular mechanisms underlying HL via systems biology approaches provides a promising option. In this study, we try to elucidate the molecular mechanisms related to the disease and identify potential pharmaceutical targets from a network-based perspective. Results We constructed a series of network models. Based on the analysis of these networks, we attempted to identify the biomarkers and elucidate the molecular mechanisms underlying HL. Initially, we built three different but related protein networks, i.e., background network, HL-basic network and HL-specific network. By analyzing these three networks, we investigated the connection characteristic of the HL-related proteins. Subsequently, we explored the miRNA regulation on HL-specific network and analyzed three kinds of simple regulation patterns, i.e., co-regulation of protein pairs, as well as the direct and indirect regulation of triple proteins. Finally, we constructed a simplified protein network combined with the regulation of miRNAs on proteins to better understand the relation between HL-related proteins and miRNAs. Conclusions We find that the HL-related proteins are more likely to connect with each other compared to other proteins. Moreover, the HL-specific network can be further divided into five sub-networks and 49 proteins as the backbone of HL-specific network make up and connect these 5 sub-networks. Thus, they may be closely associated with HL. In addition, we find that the co-regulation of protein pairs is the main regulatory pattern of miRNAs on the protein network in the HL-specific network. According to the regulation of miRNA on protein network, we have identified 5 core miRNAs as the potential biomarkers for diagnostic of HL. Finally, several protein pathways have been identified to closely associated with HL, which provides deep insights into underlying mechanism of HL.
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spelling doaj.art-723844f4fee2444eb022c1a2211e41672022-12-21T19:22:02ZengBMCBMC Bioinformatics1471-21052019-09-0120111310.1186/s12859-019-3041-9Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphomaHuimin Lei0Wenxu Liu1Jiarui Si2Ju Wang3Tao Zhang4School of Biomedical Engineering, Tianjin Medical UniversitySchool of Biomedical Engineering, Tianjin Medical UniversitySchool of Basic Medicine, Tianjin Medical UniversitySchool of Biomedical Engineering, Tianjin Medical UniversitySchool of Biomedical Engineering, Tianjin Medical UniversityAbstract Background Hodgkin Lymphoma (HL) is a type of aggressive malignancy in lymphoma that has high incidence in young adults and elderly patients. Identification of reliable diagnostic markers and efficient therapeutic targets are especially important for the diagnosis and treatment of HL. Although many HL-related molecules have been identified, our understanding on the molecular mechanisms underlying the disease is still far from complete due to its complex and heterogeneous characteristics. In such situation, exploring the molecular mechanisms underlying HL via systems biology approaches provides a promising option. In this study, we try to elucidate the molecular mechanisms related to the disease and identify potential pharmaceutical targets from a network-based perspective. Results We constructed a series of network models. Based on the analysis of these networks, we attempted to identify the biomarkers and elucidate the molecular mechanisms underlying HL. Initially, we built three different but related protein networks, i.e., background network, HL-basic network and HL-specific network. By analyzing these three networks, we investigated the connection characteristic of the HL-related proteins. Subsequently, we explored the miRNA regulation on HL-specific network and analyzed three kinds of simple regulation patterns, i.e., co-regulation of protein pairs, as well as the direct and indirect regulation of triple proteins. Finally, we constructed a simplified protein network combined with the regulation of miRNAs on proteins to better understand the relation between HL-related proteins and miRNAs. Conclusions We find that the HL-related proteins are more likely to connect with each other compared to other proteins. Moreover, the HL-specific network can be further divided into five sub-networks and 49 proteins as the backbone of HL-specific network make up and connect these 5 sub-networks. Thus, they may be closely associated with HL. In addition, we find that the co-regulation of protein pairs is the main regulatory pattern of miRNAs on the protein network in the HL-specific network. According to the regulation of miRNA on protein network, we have identified 5 core miRNAs as the potential biomarkers for diagnostic of HL. Finally, several protein pathways have been identified to closely associated with HL, which provides deep insights into underlying mechanism of HL.http://link.springer.com/article/10.1186/s12859-019-3041-9Protein interaction networkNetwork analysismiRNA regulationHodgkin Lymphoma
spellingShingle Huimin Lei
Wenxu Liu
Jiarui Si
Ju Wang
Tao Zhang
Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma
BMC Bioinformatics
Protein interaction network
Network analysis
miRNA regulation
Hodgkin Lymphoma
title Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma
title_full Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma
title_fullStr Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma
title_full_unstemmed Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma
title_short Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma
title_sort analyzing the regulation of mirnas on protein protein interaction network in hodgkin lymphoma
topic Protein interaction network
Network analysis
miRNA regulation
Hodgkin Lymphoma
url http://link.springer.com/article/10.1186/s12859-019-3041-9
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AT juwang analyzingtheregulationofmirnasonproteinproteininteractionnetworkinhodgkinlymphoma
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