Review Volume 12, Issue 1 pp 996—1010
Long non-coding RNA RNF7 promotes the cardiac fibrosis in rat model via miR-543/THBS1 axis and TGFβ1 activation
- 1 Department of Cardiology, Zhuzhou Hospital, The Affiliated Hospital of Xiangya Medical College of Central South University, Changsha, Hunan, China
received: July 16, 2019 ; accepted: November 8, 2019 ; published: January 8, 2020 ;https://doi.org/10.18632/aging.102463
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Copyright © 2020 Ouyang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cardiac fibrosis (CF) is regulated by multiple factors, including transforming growth factor β1 (TGFβ1) and non-coding RNAs. Thrombospondin 1 (TSP1) is a physiologic regulator of TGFβ activation. Here, we performed microarray analyses on mRNAs and lncRNAs differentially-expressed in the CF and normal rat hearts. KEGG signaling annotation and GO enrichment analyses were performed to validate the roles of extracellular matrix (ECM) and TSP1-enhanced TGFβ activation in CF. The co-expression network between differentially-expressed lncRNAs and ECM-related factors was constructed to identify candidate lncRNAs and miRNAs. We found that lncRNA Homo sapiens ring finger protein 7 (lnc RNF7) was significantly correlated with TSP1 and ECM. Lnc RNF7 silence could attenuate isoproterenol (ISP)-induced CF in rat heart in vivo and in rat cardiac fibroblasts in vitro. Moreover, angiotensin II (Ang II) -induced CF in rat cardiac fibroblasts could also be attenuated by Lnc RNF7 silence. Furthermore, miR-543 could simultaneously target lnc RNF7 and 3' UTR of TSP1. Lnc RNF7 silence suppressed, while miR-543 inhibition promoted TSP1 protein and TGFβ activation, as well as ECM markers expression. The effects of lnc RNF7 silence was significantly reversed by miR-543 inhibition. In conclusion, CF progression might be regulated by lnc RNF7/miR-543 axis via TSP1-mediated TGFβ activation.
CF: Cardiac fibrosis; ECM: excessive extracellular matrix; ISP: isoproterenol; TGFβ1: transforming growth factor β1; Ang II: angiotensin II; TSP1: Thrombospondin 1; lncRNAs: long noncoding RNAs; lnc RNF7: lncRNA Homo sapiens ring finger protein 7; ceRNAs: competing endogenous RNAs; CHRF: LncRNA cardiac hypertrophy-related factor; CARL: LncRNA cardiac apoptosis-related lncRNA; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: Gene Ontology; RIP: RNA binding protein Immunoprecipitation; AGO2: Argonaute 2.