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.102705How to Cite
Abstract
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.