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Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN

Background: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying...

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Autores principales: Li, Zhiqiang, Li, Hongqiang, Liu, Baoxin, Luo, Jiachen, Qin, Xiaoming, Gong, Mengmeng, Shi, Beibei, Wei, Yidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330660/
https://www.ncbi.nlm.nih.gov/pubmed/32624698
http://dx.doi.org/10.7150/ijms.41980
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author Li, Zhiqiang
Li, Hongqiang
Liu, Baoxin
Luo, Jiachen
Qin, Xiaoming
Gong, Mengmeng
Shi, Beibei
Wei, Yidong
author_facet Li, Zhiqiang
Li, Hongqiang
Liu, Baoxin
Luo, Jiachen
Qin, Xiaoming
Gong, Mengmeng
Shi, Beibei
Wei, Yidong
author_sort Li, Zhiqiang
collection PubMed
description Background: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism. Methods: Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage. Results: As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis in vitro and in vivo. miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells. Conclusion: In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression.
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spelling pubmed-73306602020-07-02 Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN Li, Zhiqiang Li, Hongqiang Liu, Baoxin Luo, Jiachen Qin, Xiaoming Gong, Mengmeng Shi, Beibei Wei, Yidong Int J Med Sci Research Paper Background: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism. Methods: Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage. Results: As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis in vitro and in vivo. miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells. Conclusion: In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression. Ivyspring International Publisher 2020-06-05 /pmc/articles/PMC7330660/ /pubmed/32624698 http://dx.doi.org/10.7150/ijms.41980 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
Li, Zhiqiang
Li, Hongqiang
Liu, Baoxin
Luo, Jiachen
Qin, Xiaoming
Gong, Mengmeng
Shi, Beibei
Wei, Yidong
Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN
title Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN
title_full Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN
title_fullStr Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN
title_full_unstemmed Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN
title_short Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN
title_sort inhibition of mir-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and dna damage by targeting pten
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330660/
https://www.ncbi.nlm.nih.gov/pubmed/32624698
http://dx.doi.org/10.7150/ijms.41980
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