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Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α

Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular adaptive response to hypoxia. Accumulating evidence shows that HIF-1 induces some non-coding RNAs (ncRNAs) including lncRNAs and miRNAs to modulate its own activity, enclosing several feedback loops. How the two classes of ncRNAs ar...

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Autores principales: Sun, Cheng-Yuan, Zhang, Xiao-Peng, Liu, Feng, Wang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461903/
https://www.ncbi.nlm.nih.gov/pubmed/32973869
http://dx.doi.org/10.3389/fgene.2020.00871
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author Sun, Cheng-Yuan
Zhang, Xiao-Peng
Liu, Feng
Wang, Wei
author_facet Sun, Cheng-Yuan
Zhang, Xiao-Peng
Liu, Feng
Wang, Wei
author_sort Sun, Cheng-Yuan
collection PubMed
description Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular adaptive response to hypoxia. Accumulating evidence shows that HIF-1 induces some non-coding RNAs (ncRNAs) including lncRNAs and miRNAs to modulate its own activity, enclosing several feedback loops. How the two classes of ncRNAs are orchestrated in the HIF-1-dependent adaptive response to hypoxia is poorly understood. By selecting lincRNA-p21 and miR-155 as the representatives, we develop an integrated model of the HIF-1 network comprising interlinked positive and negative feedback loops to clarify the interplay between the two ncRNAs in the hypoxic response. By numerical simulations, we find that coordination of lincRNA-p21 and miR-155 shapes the adaptive dynamics of HIF-1α: lincRNA-p21 induction in the early phase stimulates the upregulation of HIF-1α via stabilizing it, while miR-155 induction in the late phase promotes the recovery of HIF-1α via enhancing the degradation of its mRNA. Moreover, HIF-1α-induced PHD2 plays an auxiliary role in the decline of HIF-1α. In addition, lincRNA-p21 and miR-155 modulate each other via regulating HIF-1α activity. Together, lincRNA-p21 and miR-155 coordinate in modulating HIF-1α dynamics, and our work may shed light on the role for ncRNAs in the cellular adaptation to hypoxia.
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spelling pubmed-74619032020-09-23 Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α Sun, Cheng-Yuan Zhang, Xiao-Peng Liu, Feng Wang, Wei Front Genet Genetics Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular adaptive response to hypoxia. Accumulating evidence shows that HIF-1 induces some non-coding RNAs (ncRNAs) including lncRNAs and miRNAs to modulate its own activity, enclosing several feedback loops. How the two classes of ncRNAs are orchestrated in the HIF-1-dependent adaptive response to hypoxia is poorly understood. By selecting lincRNA-p21 and miR-155 as the representatives, we develop an integrated model of the HIF-1 network comprising interlinked positive and negative feedback loops to clarify the interplay between the two ncRNAs in the hypoxic response. By numerical simulations, we find that coordination of lincRNA-p21 and miR-155 shapes the adaptive dynamics of HIF-1α: lincRNA-p21 induction in the early phase stimulates the upregulation of HIF-1α via stabilizing it, while miR-155 induction in the late phase promotes the recovery of HIF-1α via enhancing the degradation of its mRNA. Moreover, HIF-1α-induced PHD2 plays an auxiliary role in the decline of HIF-1α. In addition, lincRNA-p21 and miR-155 modulate each other via regulating HIF-1α activity. Together, lincRNA-p21 and miR-155 coordinate in modulating HIF-1α dynamics, and our work may shed light on the role for ncRNAs in the cellular adaptation to hypoxia. Frontiers Media S.A. 2020-08-18 /pmc/articles/PMC7461903/ /pubmed/32973869 http://dx.doi.org/10.3389/fgene.2020.00871 Text en Copyright © 2020 Sun, Zhang, Liu and Wang. 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 Genetics
Sun, Cheng-Yuan
Zhang, Xiao-Peng
Liu, Feng
Wang, Wei
Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α
title Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α
title_full Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α
title_fullStr Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α
title_full_unstemmed Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α
title_short Orchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α
title_sort orchestration of lincrna-p21 and mir-155 in modulating the adaptive dynamics of hif-1α
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461903/
https://www.ncbi.nlm.nih.gov/pubmed/32973869
http://dx.doi.org/10.3389/fgene.2020.00871
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