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MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter

MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been doc...

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Autores principales: Pan, Lei, Huang, Bi-Jun, Ma, Xiu-E, Wang, Shi-Yi, Feng, Jing, Lv, Fei, Liu, Yuan, Liu, Yi, Li, Chang-Ming, Liang, Dan-Dan, Li, Jun, Xu, Liang, Chen, Yi-Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394484/
https://www.ncbi.nlm.nih.gov/pubmed/25764156
http://dx.doi.org/10.3390/ijms16035420
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author Pan, Lei
Huang, Bi-Jun
Ma, Xiu-E
Wang, Shi-Yi
Feng, Jing
Lv, Fei
Liu, Yuan
Liu, Yi
Li, Chang-Ming
Liang, Dan-Dan
Li, Jun
Xu, Liang
Chen, Yi-Han
author_facet Pan, Lei
Huang, Bi-Jun
Ma, Xiu-E
Wang, Shi-Yi
Feng, Jing
Lv, Fei
Liu, Yuan
Liu, Yi
Li, Chang-Ming
Liang, Dan-Dan
Li, Jun
Xu, Liang
Chen, Yi-Han
author_sort Pan, Lei
collection PubMed
description MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H(2)O(2), and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H(2)O(2)-induced elevation of mitochondrial Ca(2+) concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.
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spelling pubmed-43944842015-05-21 MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter Pan, Lei Huang, Bi-Jun Ma, Xiu-E Wang, Shi-Yi Feng, Jing Lv, Fei Liu, Yuan Liu, Yi Li, Chang-Ming Liang, Dan-Dan Li, Jun Xu, Liang Chen, Yi-Han Int J Mol Sci Article MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H(2)O(2), and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H(2)O(2)-induced elevation of mitochondrial Ca(2+) concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes. MDPI 2015-03-10 /pmc/articles/PMC4394484/ /pubmed/25764156 http://dx.doi.org/10.3390/ijms16035420 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pan, Lei
Huang, Bi-Jun
Ma, Xiu-E
Wang, Shi-Yi
Feng, Jing
Lv, Fei
Liu, Yuan
Liu, Yi
Li, Chang-Ming
Liang, Dan-Dan
Li, Jun
Xu, Liang
Chen, Yi-Han
MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter
title MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter
title_full MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter
title_fullStr MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter
title_full_unstemmed MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter
title_short MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter
title_sort mir-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394484/
https://www.ncbi.nlm.nih.gov/pubmed/25764156
http://dx.doi.org/10.3390/ijms16035420
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