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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Frontiers Media S.A.
2020-09-01
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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. |
first_indexed | 2024-12-14T20:18:28Z |
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language | English |
last_indexed | 2024-12-14T20:18:28Z |
publishDate | 2020-09-01 |
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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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