Circular RNAs (circRNAs) participate in regulating gene expression in diverse biological and pathological processes. The present study aimed to investigate the mechanism underlying the modulation of circRNA_000203 on expressions of fibrosis-associated genes in cardiac fibroblasts. CircRNA_000203 was shown upregulated in the diabetic mouse myocardium and in Ang-II-induced mouse cardiac fibroblasts. Enforced-expression of circRNA_000203 could increase expressions of Col1a2, Col3a1 and α-SMA in mouse cardiac fibroblasts. RNA pull-down and RT-qPCR assay indicated that circRNA_000203 could specifically sponge miR-26b-5p. Dual luciferase reporter assay revealed that miR-26b-5p interacted with 3′UTRs of Col1a2 and CTGF, and circ_000203 could block the interactions of miR-26b-5p and 3′UTRs of Col1a2 and CTGF. Transfection of miR-26b-5p could post-transcriptionaly inhibit expressions of Col1a2 and CTGF, accompanied with the suppressions of Col3a1 and α-SMA in cardiac fibroblasts. Additionally, over-expression of circRNA_000203 could eliminate the anti-fibrosis effect of miR-26b-5p in cardiac fibroblasts. Together, our results reveal that suppressing the function of miR-26b-5p contributes to the pro-fibrosis effect of circRNA_000203 in cardiac fibroblasts.
Hsp60 is an important component of defense mechanisms against diabetic myocardial injury; however, the cause of Hsp60 reduction in the diabetic myocardium remains unknown. After stimulation of cardiomyocytes with high glucose in vivo and in vitro, significant up-regulation of miR-1/miR-206 and post-transcriptional modulation of Hsp 60 were observed. Serum response factor (SRF) and the MEK1/2 pathway were involved in miR-1 and miR-206 expression in cardiomyocytes. miR-1 and miR-206 regulated Hsp60 expression post-transcriptionally and accelerated cardiomyocyte apoptosis through Hsp60. These results revealed that miR-1 and miR-206 regulate Hsp60 expression, contributing to high glucose-mediated apoptosis in cardiomyocytes.
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