A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction.
Sci Rep
; 8(1): 14638, 2018 10 02.
Article
in En
| MEDLINE
| ID: mdl-30279543
ABSTRACT
This study identified microRNAs involved in myocardial infarction (MI) through a novel system-level approach using RNA sequencing data in an MI mouse model. This approach involved the extraction of DEGs and DEmiRs from RNA-seq data in sham and MI samples and the subsequent selection of two miRNAs miR-30-5p (family) and miR-142a-5p, which were downregulated and upregulated in MI, respectively. Gene Set Enrichment Analysis (GSEA) using the predicted targets of the two miRNAs suggested that apoptosis is an essential gene ontology (GO)-associated term. In vitro functional assays using neonatal rat ventricular myocytes (NRVMs) demonstrated that miR-30-5p is anti-apoptotic and miR-142a-5p is pro-apoptotic. Luciferase assays showed that the apoptotic genes, Picalm and Skil, and the anti-apoptotic genes, Ghr and Kitl, are direct targets of miR-30-5p and miR-142a-5p, respectively. siRNA studies verified the results of the luciferase assays for target validation. The results of the system-level high throughput approach identified a pair of functionally antagonistic miRNAs and their targets in MI. This study provides an in-depth analysis of the role of miRNAs in the pathogenesis of MI which could lead to the development of therapeutic tools. The system-level approach could be used to identify miRNAs involved in variety of other diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apoptosis
/
Myocytes, Cardiac
/
MicroRNAs
/
Myocardial Infarction
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2018
Document type:
Article