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MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases, which is often accompanied with structural and electrical remodeling, and can even lead to sudden cardiac death. However, its molecular mechanism still remains largely unknown. Here, we induced cardiomyocyte hyp...

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Autores principales: Cao, Xuefeng, Zhang, Zheng, Wang, Yu, Shan, Weichao, Wang, Ruiting, Mao, Shufang, Ding, Shi, Pang, Chong, Li, Baoqun, Zhou, Jian, Guo, Xiaoyan, Guo, Na, Li, Cui, Liang, Jing, Ma, Wenya, Liu, Yu, Zhao, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263894/
https://www.ncbi.nlm.nih.gov/pubmed/34248630
http://dx.doi.org/10.3389/fphar.2021.680349
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author Cao, Xuefeng
Zhang, Zheng
Wang, Yu
Shan, Weichao
Wang, Ruiting
Mao, Shufang
Ding, Shi
Pang, Chong
Li, Baoqun
Zhou, Jian
Guo, Xiaoyan
Guo, Na
Li, Cui
Liang, Jing
Ma, Wenya
Liu, Yu
Zhao, Liang
author_facet Cao, Xuefeng
Zhang, Zheng
Wang, Yu
Shan, Weichao
Wang, Ruiting
Mao, Shufang
Ding, Shi
Pang, Chong
Li, Baoqun
Zhou, Jian
Guo, Xiaoyan
Guo, Na
Li, Cui
Liang, Jing
Ma, Wenya
Liu, Yu
Zhao, Liang
author_sort Cao, Xuefeng
collection PubMed
description Cardiac hypertrophy is a common pathological process of various cardiovascular diseases, which is often accompanied with structural and electrical remodeling, and can even lead to sudden cardiac death. However, its molecular mechanism still remains largely unknown. Here, we induced cardiomyocyte hypertrophy by angiotensin II (Ang II), and found that miR-27a-3p and hypertrophy-related genes were up-regulated. Further studies showed that miR-27a-3p-inhibitor can alleviate myocardial hypertrophy and electrical remodeling. Moreover, luciferase assay confirmed that miR-27a-3p could regulate the expression of downstream Hoxa10 at the transcriptional level by targeting at its 3′UTR. At the same time, the protein expression of Hoxa10 was significantly reduced in Ang II-treated cardiomyocytes. Furthermore, overexpression of Hoxa10 can reverse myocardial hypertrophy and electrical remodeling induced by Ang II in cardiomyocytes. Finally, we found that Hoxa10 positively regulated the expression of potassium channel protein Kv4.3 which was down-regulated in hypertrophic cardiomyocytes. Taken together, our results revealed miR-27a-3p/Hoxa10/Kv4.3 axis as a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which provided a new target for clinical prevention and treatment of cardiac hypertrophy and heart failure.
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spelling pubmed-82638942021-07-09 MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression Cao, Xuefeng Zhang, Zheng Wang, Yu Shan, Weichao Wang, Ruiting Mao, Shufang Ding, Shi Pang, Chong Li, Baoqun Zhou, Jian Guo, Xiaoyan Guo, Na Li, Cui Liang, Jing Ma, Wenya Liu, Yu Zhao, Liang Front Pharmacol Pharmacology Cardiac hypertrophy is a common pathological process of various cardiovascular diseases, which is often accompanied with structural and electrical remodeling, and can even lead to sudden cardiac death. However, its molecular mechanism still remains largely unknown. Here, we induced cardiomyocyte hypertrophy by angiotensin II (Ang II), and found that miR-27a-3p and hypertrophy-related genes were up-regulated. Further studies showed that miR-27a-3p-inhibitor can alleviate myocardial hypertrophy and electrical remodeling. Moreover, luciferase assay confirmed that miR-27a-3p could regulate the expression of downstream Hoxa10 at the transcriptional level by targeting at its 3′UTR. At the same time, the protein expression of Hoxa10 was significantly reduced in Ang II-treated cardiomyocytes. Furthermore, overexpression of Hoxa10 can reverse myocardial hypertrophy and electrical remodeling induced by Ang II in cardiomyocytes. Finally, we found that Hoxa10 positively regulated the expression of potassium channel protein Kv4.3 which was down-regulated in hypertrophic cardiomyocytes. Taken together, our results revealed miR-27a-3p/Hoxa10/Kv4.3 axis as a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which provided a new target for clinical prevention and treatment of cardiac hypertrophy and heart failure. Frontiers Media S.A. 2021-06-24 /pmc/articles/PMC8263894/ /pubmed/34248630 http://dx.doi.org/10.3389/fphar.2021.680349 Text en Copyright © 2021 Cao, Zhang, Wang, Shan, Wang, Mao, Ding, Pang, Li, Zhou, Guo, Guo, Li, Liang, Ma, Liu and Zhao. https://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 Pharmacology
Cao, Xuefeng
Zhang, Zheng
Wang, Yu
Shan, Weichao
Wang, Ruiting
Mao, Shufang
Ding, Shi
Pang, Chong
Li, Baoqun
Zhou, Jian
Guo, Xiaoyan
Guo, Na
Li, Cui
Liang, Jing
Ma, Wenya
Liu, Yu
Zhao, Liang
MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression
title MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression
title_full MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression
title_fullStr MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression
title_full_unstemmed MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression
title_short MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression
title_sort mir-27a-3p/hoxa10 axis regulates angiotensin ii-induced cardiomyocyte hypertrophy by targeting kv4.3 expression
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263894/
https://www.ncbi.nlm.nih.gov/pubmed/34248630
http://dx.doi.org/10.3389/fphar.2021.680349
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