Research Paper Volume 12, Issue 2 pp 1643—1655
Hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3
- 1 Second Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- 2 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- 3 Sparkfire Scientific Research Group of Nanjing Medical University, Nanjing, China
- 4 Department of Gastroenterology, Fengxian Hospital, Southern Medical University, Shanghai, China
- 5 Department of Gastroenterology, Shanghai Sixth People’s Hospital (South), Shanghai Jiaotong University, Shanghai, China
- 6 Department of Liver Diseases, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, China
received: February 16, 2019 ; accepted: January 2, 2020 ; published: January 29, 2020 ;https://doi.org/10.18632/aging.102705
How to Cite
Copyright © 2020 Ji 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.
Previous circular RNA (circRNA) microarray analyses have uncovered an abnormal expression of hsa_circ_0070963 in hepatic stellate cells (HSCs). However, the specific role of hsa_circ_0070963 in liver fibrosis remains unknown. Here, we show that hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3. Moreover, we demonstrated that hsa_circ_0070963 levels were reduced during liver fibrosis while restoring hsa_circ_0070963 levels abolished HSC activation, with a reduction in α-SMA and type I collagen levels both in vitro and in vivo. Furthermore, hsa_circ_0070963 overexpression suppressed both cell proliferation and the cell cycle of HSCs. MiR-223-3p was confirmed as a target of hsa_circ_0070963 and was shown to be involved in the effects of hsa_circ_0070963 on HSC activation. Furthermore, LEMD3 was confirmed as a target of miR-223-3p and was shown to be responsible for the activation of HSCs. The interactions between hsa_circ_0070963, miR-223-3p, and LEMD3 were validated via bioinformatic analysis, luciferase reporter assays, and rescue experiments. Collectively, hsa_circ_0070963 appeared to function as a miR-223-3p sponge that inhibited HSC activation in liver fibrosis via regulation of miR-223-3p and LEMD3. Therefore, hsa_circ_0070963 may serve as a potential therapeutic target for liver fibrosis.