miR-29-TET2 Inhibits Lipid Accumulation in Hepatocytes by Activating the Autophagy Pathway
10.13865/j.cnki.cjbmb.2025.03.1021
- VernacularTitle:miR-29-TET2通过激活自噬抑制肝细胞脂质积累
- Author:
Rui-Li SHEN
1
;
Han-Bing LI
;
Yu-Wei FAN
;
Ni-Hong CHENG
;
Wen-Jing WU
;
Jin ZHANG
Author Information
1. 浙江工业大学药学院,杭州 310000;嘉兴大学生物与化学工程学院,浙江嘉兴 314001
- Publication Type:Journal Article
- Keywords:
microRNA-29(miR-29);
non-alcoholic fatty liver disease(NAFLD);
accumulation of lip-ids;
autophagy
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(5):696-706
- CountryChina
- Language:Chinese
-
Abstract:
The incidence of non-alcoholic fatty liver disease(NAFLD)has been increasing annually.Current primary treatment strategies involve dietary modifications and increased physical activity to allevi-ate symptoms,yet there is a notable lack of targeted pharmacological interventions.Members of the micro RNA-29(miR-29)family(miR-29a,miR-29b,miR-29c)are known to play a critical regulatory role in lipid metabolism within hepatocytes;however,the underlying mechanisms remain to be elucidated.This study aims to identify the target genes and associated signaling pathways of the miR-29 family,thereby providing potential therapeutic targets for the development of NAFLD treatments.Firstly,the human liver cell line HepG2 was utilized as a model for adipogenic induction,and miR-29a/b/c-3p mimics were indi-vidually transfected.Through methods such as Oil Red O staining and triglyceride(TG)quantification,it was observed that the miR-29 family members significantly inhibited lipid accumulation in hepatocytes(P＜0.05).Subsequently,qRT-PCR and Western blot were utilized to detect the expression levels of ad-ipogenic marker genes(fatty acid synthase(FAS),acetyl coa carboxylase(ACACA),stearoyl-coen-zyme a desaturase 1(Scd 1))and autophagy marker genes(sequestosome 1(SQSTM1,also known as p62),autophagy related gene 5(Atg5)),and the results indicated that the members of the miR-29 fam-ily could significantly suppress the expression of FAS,ACACA,Scd1,and p62 genes in hepatocytes,while significantly enhancing the level of the Atg5 gene.Further investigations using signaling pathway activity analysis and dual luciferase reporter assays confirmed that the miR-29a/b/c could suppress the mTOR signaling pathway activity and directly interact with the ten-eleven translocation 2(TET2)gene.Finally,co-transfection experiments were performed to examine the potential synergistic effects among the miR-29-3p family members,and the results demonstrated that co-transfection of miR-29 family members more effectively inhibited lipid droplet accumulation in HepG2 cells and further suppressed the expression of the target gene TET2 compared to individual transfection.In summary,the miR-29 family members may reduce lipid accumulation in hepatocytes by inhibiting the mTOR signaling pathway via the TET2 gene,and they exhibit a positive synergistic effect.
