Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer

Non-coding RNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be indispensable factors in carcinogenesis and cancer development. Numerous studies have explored the regulatory functions of these molecules and identified the synergistic interactions among lncRNAs or...

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Main Authors: Bin Zhao, Xiusheng Qu, Xin Lv, Qingdong Wang, Deqiang Bian, Fan Yang, Xingwang Zhao, Zhiwu Ji, Jian Ni, Yan Fu, Guorong Xin, Haitao Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.572983/full
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author Bin Zhao
Xiusheng Qu
Xin Lv
Qingdong Wang
Deqiang Bian
Fan Yang
Xingwang Zhao
Zhiwu Ji
Jian Ni
Yan Fu
Guorong Xin
Haitao Yu
author_facet Bin Zhao
Xiusheng Qu
Xin Lv
Qingdong Wang
Deqiang Bian
Fan Yang
Xingwang Zhao
Zhiwu Ji
Jian Ni
Yan Fu
Guorong Xin
Haitao Yu
author_sort Bin Zhao
collection DOAJ
description Non-coding RNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be indispensable factors in carcinogenesis and cancer development. Numerous studies have explored the regulatory functions of these molecules and identified the synergistic interactions among lncRNAs or miRNAs, while those between lncRNAs and miRNAs remain to be investigated. In this study, we constructed and characterized an lncRNA–miRNA synergistic network following a four-step approach by integrating the regulatory pairs and expression profiles. The synergistic interactions with more shared regulatory mRNAs were found to have higher interactional intensity. Through the analysis of nodes in the network, we found that lncRNAs played roles that are more central and had similar synergistic interactions with their neighbors when compared with miRNAs. In addition, known colon adenocarcinoma (COAD)-related RNAs were found to be enriched in this synergistic network, with higher degrees, betweenness, and closeness. Finally, we proposed a risk score model to predict the clinical outcome for COAD patients based on two prognostic hub lncRNAs, MEG3 and ZEB1-AS1. Moreover, the hierarchical networks of these two lncRNAs could contribute to the understanding of the biological mechanism of tumorigenesis. For each lncRNA–miRNA interaction in the hub-related subnetwork and two hierarchical networks, we performed RNAup method to evaluate their binding energy. Our results identified two important lncRNAs with prognostic roles in colon cancer and dissected their regulatory mechanism involving synergistic interaction with miRNAs.
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spelling doaj.art-a2353263006c4633a7e829af1587e3aa2022-12-21T22:48:48ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-09-011110.3389/fgene.2020.572983572983Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon CancerBin Zhao0Xiusheng Qu1Xin Lv2Qingdong Wang3Deqiang Bian4Fan Yang5Xingwang Zhao6Zhiwu Ji7Jian Ni8Yan Fu9Guorong Xin10Haitao Yu11Department of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Chemoradiotherapy, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of General Surgery, Samii Medical Center, Shenzhen, ChinaDepartment of Anesthesiology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaScientific Research Departments, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaDepartment of Proctology, First Affiliated Hospital of Jiamusi University, Jiamusi, ChinaNon-coding RNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be indispensable factors in carcinogenesis and cancer development. Numerous studies have explored the regulatory functions of these molecules and identified the synergistic interactions among lncRNAs or miRNAs, while those between lncRNAs and miRNAs remain to be investigated. In this study, we constructed and characterized an lncRNA–miRNA synergistic network following a four-step approach by integrating the regulatory pairs and expression profiles. The synergistic interactions with more shared regulatory mRNAs were found to have higher interactional intensity. Through the analysis of nodes in the network, we found that lncRNAs played roles that are more central and had similar synergistic interactions with their neighbors when compared with miRNAs. In addition, known colon adenocarcinoma (COAD)-related RNAs were found to be enriched in this synergistic network, with higher degrees, betweenness, and closeness. Finally, we proposed a risk score model to predict the clinical outcome for COAD patients based on two prognostic hub lncRNAs, MEG3 and ZEB1-AS1. Moreover, the hierarchical networks of these two lncRNAs could contribute to the understanding of the biological mechanism of tumorigenesis. For each lncRNA–miRNA interaction in the hub-related subnetwork and two hierarchical networks, we performed RNAup method to evaluate their binding energy. Our results identified two important lncRNAs with prognostic roles in colon cancer and dissected their regulatory mechanism involving synergistic interaction with miRNAs.https://www.frontiersin.org/article/10.3389/fgene.2020.572983/fullnon-coding RNAsynergistic interactioncolon cancerbiological mechanismprognostic biomarker
spellingShingle Bin Zhao
Xiusheng Qu
Xin Lv
Qingdong Wang
Deqiang Bian
Fan Yang
Xingwang Zhao
Zhiwu Ji
Jian Ni
Yan Fu
Guorong Xin
Haitao Yu
Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer
Frontiers in Genetics
non-coding RNA
synergistic interaction
colon cancer
biological mechanism
prognostic biomarker
title Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer
title_full Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer
title_fullStr Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer
title_full_unstemmed Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer
title_short Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer
title_sort construction and characterization of a synergistic lncrna mirna network reveals a crucial and prognostic role of lncrnas in colon cancer
topic non-coding RNA
synergistic interaction
colon cancer
biological mechanism
prognostic biomarker
url https://www.frontiersin.org/article/10.3389/fgene.2020.572983/full
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