MiR-31a-5p protects myocardial cells against apoptosis by targeting Tp53.
Mol Med Rep
; 17(3): 3898-3904, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29286111
ABSTRACT
The pathogenesis and progression of heart failure (HF) involves multiple mechanisms, including the increased activity of the renin-angiotensin-aldosterone system, apoptosis and differential expression of microRNAs (miRNAs/miRs). Our previous study revealed an increase in miR31a5p levels in the failing hearts of a rat HF model. In the present study, whether and how miR31a5p mediates angiotensin II (AngII)induced apoptosis in the cardiac H9C2 cell line, was investigated using molecular biological approaches, including reverse transcription followed by quantitative polymerase chain reaction, western blotting, RNA arrays, and mutagenesis. It was demonstrated that AngII stimulation increased apoptosis and decreased miR31a5p expression, which coincided with increased tumor protein p53 (Tp53) levels. Overexpression of miR31a5p significantly suppressed the AngIIinduced apoptotic rate and caspase3 activity, while suppression of miR31a5p did the opposite. A total of 16 proapoptotic genes that were downregulated and 4 antiapoptotic genes that were upregulated in the miR31a5poverexpressed cells were identified. It was also revealed that Tp53 mRNA contained the seed sequence in its 3'untranslated region for miR31a5p binding. The luciferase reporter analysis showed that miR31a5p repressed the luciferase activity of the wildtype seed sequence, but not the mutated seed sequence fused to a reporter construct. Thus, it was demonstrated that miR31a5p mediated AngIItriggered apoptosis in myocardial cells at least partially through targeting Tp53. These findings advance the understanding of the functional interaction between miRNAs and Tp53 in the setting of cardiac diseases. Further work is required to explore whether miR31a5p can serve as a therapeutic target for HF treatment in vivo.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
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Proteína Supressora de Tumor p53
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Apoptose
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Miócitos Cardíacos
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MicroRNAs
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Proteínas Reguladoras de Apoptose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2018
Tipo de documento:
Article