CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease.
Lipids Health Dis
; 21(1): 127, 2022 Nov 29.
Article
in En
| MEDLINE
| ID: mdl-36443854
ABSTRACT
BACKGROUND:
Non-alcoholic fatty liver (NAFLD) is a complex metabolic disease characterized by fatty degeneration of hepatocytes. Circular RNAs (circRNAs) have been reported to be essential for (NAFLD progression. The potential mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the NAFLD was investigated in this study.METHODS:
Hepatocyte (Hepa1-6) cells treated with oleic acid/palmitic acid (OA/PA) were used as the in vitro NAFLD model, and C57BL/6 mice fed with high-fat diet (HFD) were used as the in vivo NAFLD model. The circLDLR, LDLR, and miR-667-5p expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein levels of Light Chain Microtubule-Associated Protein 3 (LC3) and Sequestosome-1(p62) was examined by western blot. The circLDLR location was confirmed using RNA fluorescence in situ hybridization. Oil red O staining was carried out to measure lipid deposition in cells. The secreted levels of triglyceride (TG) and total cholesterol (TC) were detected through Enzymatic. The existence of the circLDLR/miR-667-5p/sirtuin 1 (SIRT1) regulatory axis was validated by applying the dual-luciferase reporter assay.RESULTS:
The circLDLR expression showed a prominent down-regulation in OA/PA-treated Hepa1-6 cells, whereas the LDLR expression was up-regulated. Overexpression of circLDLR significantly attenuated lipid droplet accumulation in NAFLD models in vitro/vivo, reduced TG, TC, and p62 levels, and increased LC3-II levels and the amount of the green fluorescent protein (GFP)-LC3 puncta in cells. CircLDLR and SIRT1 are common targets of miR-667-5p to inhibit the TG and TC and promote the autophagy pathway. SIRT1 knockdown reversed the effects of circLDLR overexpression.CONCLUSIONS:
CircLDLR alleviated the development of NAFLD by inducing autophagic flux while modulating the miR-667-5p/SIRT1 axis reversed its effects, suggesting that targeting circLDLR/miR-667-5p/SIRT1 axis may be a promising therapeutic strategy for NAFLD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MicroRNAs
/
Non-alcoholic Fatty Liver Disease
Limits:
Animals
Language:
En
Journal:
Lipids Health Dis
Journal subject:
BIOQUIMICA
/
METABOLISMO
Year:
2022
Document type:
Article
Affiliation country:
China