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A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via suppressing miR-141 by targeting TGF-β1
Ist Teil von
Biochemical and biophysical research communications, 2017-06, Vol.487 (4), p.769-775
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
Circular RNAs (circRNAs) are a novel type of endogenous noncoding RNA gaining research interest in recent years. Despite this increase in interest, the mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases, particularly myocardial fibrosis, is rarely reported. In the following study, the expression profiles and potential mechanisms of circRNAs in mice myocardial fibrosis models in vitro are investigated. Previous research examining circRNA expression profiles of diabetic db/db mice myocardium using circRNA microarray found 43 circRNAs were abnormally expressed, including 24 up-regulated circRNAs and 19 down-regulated circRNAs. Furthermore, circRNA_010567 was markedly up-regulated in diabetic mice myocardium and cardiac fibroblasts (CFs) treated with Ang II. Bioinformatics analysis predicted circRNA_010567, sponge miR-141 and miR-141 directly target TGF-β1, which was validated by dual-luciferase assay. Subsequently, functional experiments revealed circRNA_010567 silencing could up-regulate miR-141 and down-regulate TGF-β1 expression, and suppress fibrosis-associated protein resection in CFs, including Col I, Col III and α-SMA. Results demonstrate the circRNA_010567/miR-141/TGF-β1 axis plays an important regulatory role in the diabetic mice myocardial fibrosis model. The present study characterizes a new function of circRNA in the pathogenesis of myocardial fibrosis in a diabetic mouse model, providing novel insight for circRNA-miRNA-mRNA in cardiovascular disease.
•A novel identified circular RNA, circRNA_010567, is up-regulated in diabetic mice myocardium.•CircRNA_010567 knockdown suppresses fibrosis-associated protein secretion in cardiac fibroblasts.•CircRNA_010567 acts as an endogenous sponge of miR-141.•miR-141 targets TGF-β1.•CircRNA_010567/miR-141/TGF-β1 axis plays an important regulation in mice myocardial fibrosis.