Aging
Navigate
Submit an Article
Research Paper|Volume 12, Issue 2|pp 1643—1655

Hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3

Dong Ji1, Guo-Feng Chen1, Jin-Cheng Wang2, Si-Han Ji2,3, Xue-Wen Wu4,5, Xiao-Jie Lu2, Jin-Lian Chen4,5, Jing-Tao Li6
  • 1Second Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
  • 2Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
  • 3Sparkfire Scientific Research Group of Nanjing Medical University, Nanjing, China
  • 4Department of Gastroenterology, Fengxian Hospital, Southern Medical University, Shanghai, China
  • 5Department of Gastroenterology, Shanghai Sixth People’s Hospital (South), Shanghai Jiaotong University, Shanghai, China
  • 6Department of Liver Diseases, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, China
* Equal contribution
Received: February 16, 2019Accepted: January 2, 2020Published: January 29, 2020
https://doi.org/10.18632/aging.102705

Copyright: © 2020 Ji et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.