miR-34b/c regulates doxorubicin-induced myocardial cell injury through ITCH.
Cell Cycle
; 18(23): 3263-3274, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31627713
ABSTRACT
Objective:
To determine the underlying mechanism of miR-34b/c in regulating doxorubicin (Dox)-induced myocardial cell injury.Methods:
The viability of mouse myocardial cells HL-1 was detected by MTT assay. The apoptosis of HL-1 cells was detected by TUNEL assay. mRNA expressions of ITCH, TNF-α and IL-6 were measured by qRT-PCR. Protein levels of ITCH, NF-κB, TNF-α and IL-6 were measured by western blot. Dual luciferase assay was performed to detect the regulation of miR-34b/c on ITCH. Mouse model of cardiomyopathy was induced by intraperitoneal injection of Dox.Results:
Dox reduced HL-1 cell viability and activated NF-κB pathway in HL-1 cells. miR-34b/c expressions were gradually up-regulated and ITCH expression was gradually down-regulated in Dox-treated HL-1 cells. miR-34b/c expression had negative correlation with the mRNA expression of ITCH. Besides, ITCH was a target of miR-34b/c. miR-34b/c mimic reduced cell viability, suppressed ITCH expression, increased TNF-α and IL-6 level, and promoted NF-κB expression in nucleus and cytoplasm of HL-1 cells. Whereas silencing miR-34 protected HL-1 cells through regulating ITCH. Finally, we demonstrated miR-34 antagomir-protected myocardial cells in mouse model of cardiomyopathy.Conclusion:
miR-34b/c decreased HL-1 cell viability and promoted the secretion of proinflammatory cytokines in Dox-induced myocardial cells through ITCH/NF-κB pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina-Proteína Ligases
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Traumatismos Cardíacos
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Cardiomiopatias
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2019
Tipo de documento:
Article