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

• Published in: Scientific reports Vol. 7; no. 1; p. 40342
• Main Authors: Tang, Chun-Mei, Zhang, Ming, Huang, Lei, Hu, Zhi-qin, Zhu, Jie-Ning, Xiao, Zhen, Zhang, Zhuo, Lin, Qiu-xiong, Zheng, Xi-Long, -Yang, Min, Wu, Shu-Lin, Cheng, Jian-Ding, Shan, Zhi-Xin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.01.2017; Nature Publishing Group
• Subjects: 13; 13/44; 38; 38/61; 42; 631/337/384/2568; 64; 64/60; 692/4019/592/75/74/1540; 82; 82/1; 82/80; Animals; Animals, Newborn; Base Sequence; Collagen Type I - metabolism; Connective tissue growth factor; Connective Tissue Growth Factor - metabolism; Diabetes mellitus; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Gene expression; Gene Expression Regulation; Heart; Heart diseases; Humanities and Social Sciences; Male; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Biological; multidisciplinary; Myocardium; Myocardium - metabolism; Myocardium - pathology; Overexpression; Post-transcription; Ribonucleic acid; RNA; RNA - genetics; RNA - metabolism; Science; Science (multidisciplinary); Transcription; Transfection; Up-Regulation - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep40342

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.