Research Paper Advance Articles pp 23996—24008
Hsa_circ_0048179 attenuates free fatty acid-induced steatosis via hsa_circ_0048179/miR-188-3p/GPX4 signaling
- 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- 2 Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- 3 Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- 4 Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32304, USA
- 5 Department of Dermatovenereology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
Received: February 25, 2020 Accepted: August 17, 2020 Published: November 18, 2020https://doi.org/10.18632/aging.104081
How to Cite
Copyright: © 2020 Yang 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.
Although circular RNAs (circRNAs) are known to play key roles in non-alcoholic fatty liver disease, much about their targets and mechanisms remains unknown. We therefore investigated the actions and mechanisms of hsa_circ_0048179 in an in vitro model of NAFLD. HepG2 cells were exposed to oleate/palmitate (2:1 ratio) for 24 h to induce intracellular lipid accumulation. Using CCK-8 assays, flow cytometry, fluorescence microscopy, western blotting, RT-qPCR, and Oil red O staining, we found that oleate/palmitate treatment reduced cell viability while increasing apoptosis and lipid accumulation in HepG2 cells. Levels of the antioxidant enzyme GPX4 were decreased in oleate/palmitate-treated HepG2 cells, and there were corresponding increases in reactive oxygen species and damage to mitochondrial cristae. Levels of hsa_circ_0048179 expression were also suppressed by oleate/palmitate treatment, and GPX4 levels were markedly increased in HepG2 cells following transfection with hsa_circ_0048179. Analysis of its mechanism revealed that hsa_circ_0048179 upregulated GPX4 levels by acting as a competitive “sponge” of miR-188-3p and that hsa_circ_0048179 attenuated oleate/palmitate-induced lipid accumulation in HepG2 cells by sponging miR-188-3p. Collectively, our findings suggest that hsa_circ_0048179 may play a key role in the pathogenesis of steatosis and may thus be a useful target for drug development.