CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts

Abstract

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.

Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis

“…The circRNA levels, being normalized against GAPDH [20, 21], were evaluated by the 2 −ΔΔCt method [22]. Triplicates were performed for each sample in three independent experiments.…”

The Role and Molecular Mechanism of Non-Coding RNAs in Pathological Cardiac Remodeling

“…Both in vitro and in vivo experiments illustrate that overexpression of Cdr1as aggravates MI injuries by sponging miR-7a and thus upregulating the levels of PARP and SP1, while miR-7a co-overexpression significantly attenuates the changes Cdr1as-induced [88]. Recently, circRNA_000203 has been identified from cardiac fibroblasts to have the pro-fibrosis effect as miR-26-5p sponge, thus blocking the interactions between miR-26-5p and its target fibrosis-associated genes Col1a2 and CTGF [89]. These proved pathways consisting of HRCR/miR-223/ARC, Cdr1as/miR-7a/ SP1 and circRNA_000203/miR-26-5p/ Col1a2, CTGF in cardiac myocytes and fibroblasts provide new therapeutic targets for the treatment of cardiac remodeling related diseases.…”

Testin was regulated by circRNA3175‐miR182 and inhibited endometrial epithelial cell apoptosis in pre‐receptive endometrium of dairy goats

“…circRNAs have been validated as gene regulators involved in a variety of physiological functions and pathological processes, and have been suggested to function as miRNA sponges (Hansen et al, ). In recent years, more and more circRNAs have been found to play important regulatory functions as miRNA sponges, including circRNA_000203 (Tang et al, ), hsa_circ_0005105 (Wu et al, ), and circRNA_100290 (Chen et al, ). Albeit, most of these findings were from circRNA studies in cancer, and none reported in the endometrium of dairy goats.…”

“…This enables them to act as molecular sponges for miRNAs and ultimately de‐repress miRNA target genes (He et al, ), hereby influencing post‐transcriptional regulation. Among circRNAs identified in humans, circRNA_000203 enhances the expression of fibrosis‐associated genes by derepressing targets of miR‐26b‐5p in cardiac fibroblasts (Tang et al, ), circRNA hsa_circ_0005105 up regulates nicotinamide phosphoribosyltransferase ( NAMPT ) expression and promotes chondrocyte extracellular matrix degradation by sponging miR‐26a (Wu, Zhang, Zhang, & Wang, ), and circRNA_100290 plays a role in oral cancer by functioning as a sponge of the miR‐29 family, which controls the expression of the cell‐cycle checkpoint regulator, CDK6 (Chen et al, ). In animals, circFUT10 reduces proliferation and facilitates differentiation of myoblasts by sponging miR‐133a (Li et al, ), and circLMO7 regulates myoblasts differentiation and survival by sponging miR‐378a‐3p (Wei et al, ).…”