title: 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.
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.|Southern Medical University, Guangzhou 510515, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Tang
authors.affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.|Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Hu
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Jie-Ning
authors.initials: JN
authors.lastname: Zhu
authors.affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.affiliation: The Libin Cardiovascular Institute of Alberta, Department of Biochemistry &Molecular Biology, The University of Calgary, Calgary, T2N 1N4, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Min
authors.initials: M
authors.lastname: -Yang
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jian-Ding
authors.initials: JD
authors.lastname: Cheng
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D024042:Collagen Type I / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis; D005786:Gene Expression Regulation; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D000079962:RNA, Circular; D015854:Up-Regulation / Q000235:genetics
chemical_list: C000619309:Col1a2 protein, mouse; D024042:Collagen Type I; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D000079962:RNA, Circular; D055513:Connective Tissue Growth Factor; D012313:RNA