miRNA-1183-targeted regulation of Bcl-2 contributes to the pathogenesis of rheumatic heart disease.
Biosci Rep
; 40(11)2020 11 27.
Article
in En
| MEDLINE
| ID: mdl-33073840
ABSTRACT
To determine whether up-regulation of miR-1183 targeting the gene for anti-apoptotic factor, B-cell lymphoma 2 (BCL-2) contributes to apoptosis in patients with rheumatic heart disease (RHD). Peripheral blood samples were isolated for miR-1183 characterization. The function of miRNA-1183 in RHD using miRNA mimic on PBMCs and THP-1 cell models. The binding of miR-1183 and Bcl-2 gene was confirmed by luciferase activity test. We also measured expression levels of BCL-2 in heart valve tissue from patients with RHD using ELISA and immunohistochemistry. In silico analysis and reporter gene assays indicated that miR-1183 directly targets the mRNA encoding BCL-2. It is found that miR-1183 binds directly to the 3'UTR of the BCL-2 mRNA and down-regulates the mRNA and protein levels of BCL-2. Overexpression of miR-1183 in RHD patients and cell lines down-regulated BCL-2 expression and induced apoptosis. With the progression of the disease, the expression of BCL-2 in the heart valve tissue of patients with RHD decreased. MiRNA-1183 is up-regulated in RHD and induces cardiac myocyte apoptosis through direct targeting and suppression of BCL-2, both of which might play important roles in RHD pathogenesis. During the compensatory period of RHD, up-regulated miR-1183 destroyed the balance of apoptosis proteins (Bax and BAK) in Bcl-2 family, enhance the apoptosis cascade reaction and reduce the anti apoptosis effect. The significantly higher expression levels of miR-1183 appear to play distinct roles in RHD pathogenesis by regulation BCL-2, possibly affecting myocardial apoptosis and remodeling in the context of RHD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rheumatic Heart Disease
/
Leukocytes, Mononuclear
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Apoptosis
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Proto-Oncogene Proteins c-bcl-2
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Myocytes, Cardiac
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MicroRNAs
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Heart Valves
Type of study:
Etiology_studies
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adult
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Biosci Rep
Year:
2020
Document type:
Article
Affiliation country: