Silencing lncRNA NEAT1 reduces nonalcoholic fatty liver fat deposition by regulating the miR-139-5p/c-Jun/SREBP-1c pathway
| Autor: | Sisi Jin, Hua-Qin Guan, Chun-Jing Lin, Juzeng Zheng, Xianfan Lin |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
lncRNA NEAT1
Specialties of internal medicine chemistry.chemical_compound Non-alcoholic Fatty Liver Disease microRNA Nonalcoholic fatty liver disease medicine Oil Red O Gene silencing Humans miR-139-5p chemistry.chemical_classification Gene knockdown Hepatology business.industry c-Jun c-jun Fatty liver Fatty acid General Medicine medicine.disease SREBP1c Lipids Cell biology MicroRNAs RC581-951 chemistry RNA Long Noncoding business Sterol Regulatory Element Binding Protein 1 |
| Zdroj: | Annals of Hepatology, Vol 27, Iss 2, Pp 100584-(2022) |
| ISSN: | 1665-2681 |
| Popis: | Introduction and Objectives : Nonalcoholic fatty liver disease (NAFLD) starts with the abnormal accumulation of lipids in the liver. Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) was reported to modulate hepatic metabolic homeostasis in NAFLD. However, little is known about the molecular mechanisms of NAFLD. Materials and Methods : To establish a NAFLD cellular model, HepG2 cells and LO2 cells were treated with 1 mM free fatty acids (FFAs) for 24 h. NEAT1, miRNA (miR)-139-5p, c-Jun and sterol-regulatory element binding protein-1c (SREBP-1c) were evaluated using qPCR. The protein levels of c-Jun, SREBP1c, acetyl-CoA carboxylase (ACC) and fatty acid synthetase (FAS) were determined using western blotting. Moreover, Oil Red O staining was employed to assess lipid accumulation. In addition, a kit assay was performed to evaluate TG levels. Finally, the interactions among NEAT1, miR-139-5p, c-Jun and SREBP1c were identified by dual luciferase reporter gene assay. Results : NEAT1, c-Jun and SREBP1c expression was markedly elevated, while miR-139-5p expression was reduced in the NAFLD cellular model. NEAT1 knockdown restrained lipid accumulation in the NAFLD cellular model by directly targeting miR-139-5p. Moreover, miR-139-5p overexpression suppressed lipid accumulation by directly suppressing c-Jun expression. In addition, c-Jun silencing suppressed lipid accumulation by directly targeting SREBP1c. Finally, miR-139-5p inhibition mitigated the inhibitory effect of sh-NEAT1 on lipid accumulation. Conclusion : NEAT1 aggravated FFA-induced lipid accumulation in hepatocytes by regulating the c-Jun/SREBP1c axis by sponging miR-139-5p, indicating the potential of NEAT1 as a promising therapeutic target for NAFLD. |
| Databáze: | OpenAIRE |
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