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, 2020https://doi.org/10.18632/aging.102463
How to Cite
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.