Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback...

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Autores principales:	Fang Yan, Haihong Liu, Junjun Hao, Zengrong Liu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/abdd83adea1d4ef0b47f44404daf0fbe
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spelling	oai:doaj.org-article:abdd83adea1d4ef0b47f44404daf0fbe2021-11-18T07:05:19ZDynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.1932-620310.1371/journal.pone.0043908https://doaj.org/article/abdd83adea1d4ef0b47f44404daf0fbe2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028477/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008) and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.Fang YanHaihong LiuJunjun HaoZengrong LiuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e43908 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fang Yan Haihong Liu Junjun Hao Zengrong Liu Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.
description	MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008) and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.
format	article
author	Fang Yan Haihong Liu Junjun Hao Zengrong Liu
author_facet	Fang Yan Haihong Liu Junjun Hao Zengrong Liu
author_sort	Fang Yan
title	Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.
title_short	Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.
title_full	Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.
title_fullStr	Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.
title_full_unstemmed	Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.
title_sort	dynamical behaviors of rb-e2f pathway including negative feedback loops involving mir449.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/abdd83adea1d4ef0b47f44404daf0fbe
work_keys_str_mv	AT fangyan dynamicalbehaviorsofrbe2fpathwayincludingnegativefeedbackloopsinvolvingmir449 AT haihongliu dynamicalbehaviorsofrbe2fpathwayincludingnegativefeedbackloopsinvolvingmir449 AT junjunhao dynamicalbehaviorsofrbe2fpathwayincludingnegativefeedbackloopsinvolvingmir449 AT zengrongliu dynamicalbehaviorsofrbe2fpathwayincludingnegativefeedbackloopsinvolvingmir449
_version_	1718423998842273792

Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

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