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Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis

Overactivation of β-adrenergic receptor (β-AR) can improve cardiac function temporarily but promotes the development and mortality of heart failure (HF) in the long run. CircRNA, a member of noncoding RNAs, can tolerate digestion of exonuclease and be a chronic stimulator to cell. But the relationsh...

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Autores principales: Deng, Yunfei, Wang, Jun, Xie, Guojin, Zeng, Xiaochen, Li, Hongli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775314/
https://www.ncbi.nlm.nih.gov/pubmed/31595165
http://dx.doi.org/10.7150/ijbs.36149
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author Deng, Yunfei
Wang, Jun
Xie, Guojin
Zeng, Xiaochen
Li, Hongli
author_facet Deng, Yunfei
Wang, Jun
Xie, Guojin
Zeng, Xiaochen
Li, Hongli
author_sort Deng, Yunfei
collection PubMed
description Overactivation of β-adrenergic receptor (β-AR) can improve cardiac function temporarily but promotes the development and mortality of heart failure (HF) in the long run. CircRNA, a member of noncoding RNAs, can tolerate digestion of exonuclease and be a chronic stimulator to cell. But the relationship of circRNA with HF remains a puzzle and needs to be explored. Here, we found that circ-HIPK3 affected the concentration of Ca(2+) in cytoplasm by miR-17-3p through ADCY6 (Adenylate cyclase type 6). The increase of ADCY6 caused by circ-HIPK3 was ameliorated by miR-17-3p overexpression and vice versa, implicating the existence of circ-HIPK3 - miR-17-3p - ADCY6 axis. And further assays showed that the level of circ-HIPK3 in heart was upregulated by adrenaline via transcription factor CREB1 (cAMP responsive element-binding protein 1). Experiments in vivo showed downregulation of circ-HIPK3 can alleviate fibrosis and maintain cardiac function post MI in mice. In conclusion, the increased circ-HIPK3 can be a helper for adrenaline but was harmful for heart in the long run and might be an ideal therapeutic target of HF.
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spelling pubmed-67753142019-10-08 Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis Deng, Yunfei Wang, Jun Xie, Guojin Zeng, Xiaochen Li, Hongli Int J Biol Sci Research Paper Overactivation of β-adrenergic receptor (β-AR) can improve cardiac function temporarily but promotes the development and mortality of heart failure (HF) in the long run. CircRNA, a member of noncoding RNAs, can tolerate digestion of exonuclease and be a chronic stimulator to cell. But the relationship of circRNA with HF remains a puzzle and needs to be explored. Here, we found that circ-HIPK3 affected the concentration of Ca(2+) in cytoplasm by miR-17-3p through ADCY6 (Adenylate cyclase type 6). The increase of ADCY6 caused by circ-HIPK3 was ameliorated by miR-17-3p overexpression and vice versa, implicating the existence of circ-HIPK3 - miR-17-3p - ADCY6 axis. And further assays showed that the level of circ-HIPK3 in heart was upregulated by adrenaline via transcription factor CREB1 (cAMP responsive element-binding protein 1). Experiments in vivo showed downregulation of circ-HIPK3 can alleviate fibrosis and maintain cardiac function post MI in mice. In conclusion, the increased circ-HIPK3 can be a helper for adrenaline but was harmful for heart in the long run and might be an ideal therapeutic target of HF. Ivyspring International Publisher 2019-09-07 /pmc/articles/PMC6775314/ /pubmed/31595165 http://dx.doi.org/10.7150/ijbs.36149 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Deng, Yunfei
Wang, Jun
Xie, Guojin
Zeng, Xiaochen
Li, Hongli
Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis
title Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis
title_full Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis
title_fullStr Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis
title_full_unstemmed Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis
title_short Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis
title_sort circ-hipk3 strengthens the effects of adrenaline in heart failure by mir-17-3p - adcy6 axis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775314/
https://www.ncbi.nlm.nih.gov/pubmed/31595165
http://dx.doi.org/10.7150/ijbs.36149
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