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Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes
Gestational diabetes mellitus (GDM) is a condition associated with the onset of abnormal glucose tolerance during pregnancy. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and genes can form lncRNA-mediated feedforward loops (lnc-FFLs), which are functional network motifs that regulate a wide r...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068675/ https://www.ncbi.nlm.nih.gov/pubmed/32210913 http://dx.doi.org/10.3389/fendo.2020.00093 |
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author | Fu, Xuelian Cong, Huifang Zhao, Shuyu Li, Yan Liu, Tianyi Sun, Yuhong Lv, Nan |
author_facet | Fu, Xuelian Cong, Huifang Zhao, Shuyu Li, Yan Liu, Tianyi Sun, Yuhong Lv, Nan |
author_sort | Fu, Xuelian |
collection | PubMed |
description | Gestational diabetes mellitus (GDM) is a condition associated with the onset of abnormal glucose tolerance during pregnancy. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and genes can form lncRNA-mediated feedforward loops (lnc-FFLs), which are functional network motifs that regulate a wide range of biological processes and diseases. However, lnc-FFL network motifs have not been systematically investigated in GDM, and their role in the disease remains largely unknown. In the present study, a global lnc-FFL network was constructed and analyzed. Glycometabolism- and hormone-related lnc-FFL networks were extracted from the global network. An integrated algorithm was designed to identify dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. The patterns of dysregulated lnc-FFLs in GDM were complex. Moreover, there were strong associations between dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. Core modules were extracted from the dysregulated lnc-FFL networks in GDM and showed specific and essential functions. In addition, dysregulated lnc-FFLs could combine with ceRNAs and form more complex modules, which could play novel roles in GDM. Notably, we discovered that the dysregulated lnc-FFLs were enriched in the thyroid hormone signaling pathway. Some drug-repurposing candidates, such as hormonal drugs, could be identified based on lnc-FFLs in GDM. In summary, the present study highlighted the effect of dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM and revealed their potential for the discovery of novel biomarkers and therapeutic targets for GDM. |
format | Online Article Text |
id | pubmed-7068675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70686752020-03-24 Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes Fu, Xuelian Cong, Huifang Zhao, Shuyu Li, Yan Liu, Tianyi Sun, Yuhong Lv, Nan Front Endocrinol (Lausanne) Endocrinology Gestational diabetes mellitus (GDM) is a condition associated with the onset of abnormal glucose tolerance during pregnancy. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and genes can form lncRNA-mediated feedforward loops (lnc-FFLs), which are functional network motifs that regulate a wide range of biological processes and diseases. However, lnc-FFL network motifs have not been systematically investigated in GDM, and their role in the disease remains largely unknown. In the present study, a global lnc-FFL network was constructed and analyzed. Glycometabolism- and hormone-related lnc-FFL networks were extracted from the global network. An integrated algorithm was designed to identify dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. The patterns of dysregulated lnc-FFLs in GDM were complex. Moreover, there were strong associations between dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. Core modules were extracted from the dysregulated lnc-FFL networks in GDM and showed specific and essential functions. In addition, dysregulated lnc-FFLs could combine with ceRNAs and form more complex modules, which could play novel roles in GDM. Notably, we discovered that the dysregulated lnc-FFLs were enriched in the thyroid hormone signaling pathway. Some drug-repurposing candidates, such as hormonal drugs, could be identified based on lnc-FFLs in GDM. In summary, the present study highlighted the effect of dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM and revealed their potential for the discovery of novel biomarkers and therapeutic targets for GDM. Frontiers Media S.A. 2020-03-06 /pmc/articles/PMC7068675/ /pubmed/32210913 http://dx.doi.org/10.3389/fendo.2020.00093 Text en Copyright © 2020 Fu, Cong, Zhao, Li, Liu, Sun and Lv. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Fu, Xuelian Cong, Huifang Zhao, Shuyu Li, Yan Liu, Tianyi Sun, Yuhong Lv, Nan Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes |
title | Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes |
title_full | Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes |
title_fullStr | Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes |
title_full_unstemmed | Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes |
title_short | Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes |
title_sort | construction of glycometabolism- and hormone-related lncrna-mediated feedforward loop networks reveals global patterns of lncrnas and drug repurposing in gestational diabetes |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068675/ https://www.ncbi.nlm.nih.gov/pubmed/32210913 http://dx.doi.org/10.3389/fendo.2020.00093 |
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