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Hsa_circ_0048179 attenuates free fatty acid-induced steatosis via hsa_circ_0048179/miR-188-3p/GPX4 signaling
- Source :
- Aging (Albany NY)
- Publication Year :
- 2020
- Publisher :
- Impact Journals, LLC, 2020.
-
Abstract
- 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.
- Subjects :
- Aging
Palmitates
Apoptosis
Mitochondria, Liver
GPX4
hsa_circ_0048179
miR-188-3p
chemistry.chemical_compound
medicine
Humans
Oil Red O
Viability assay
Membrane Potential, Mitochondrial
chemistry.chemical_classification
Reactive oxygen species
Chemistry
lipid accumulation
non-alcoholic fatty liver disease
Hep G2 Cells
RNA, Circular
Cell Biology
Transfection
Phospholipid Hydroperoxide Glutathione Peroxidase
medicine.disease
Molecular biology
MicroRNAs
Gene Expression Regulation
Liver
Hepatocytes
Steatosis
Reactive Oxygen Species
Intracellular
Research Paper
Oleic Acid
Signal Transduction
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....190991b682f633abaaf02bcdd7d7c4b9