LncRNA TUG1 promotes hepatic lipid accumulation by targeting the miR-29a-3p/SREBP-2/HMGCR axis in MAFLD

Metabolic-associated fatty liver disease (MAFLD) is a globally prevalent liver disorder, and long non-coding RNAs (lncRNAs) play a crucial role in its pathogenesis. However, the specific function of taurine up-regulated gene 1 (TUG1) remains incompletely understood. This study examined the molecular interactions among TUG1, miR-29a-3p, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and sterol regulatory element-binding protein 2 (SREBP-2). Two MAFLD mouse models were established, and liver damage and lipid accumulation were assessed using hematoxylin and eosin (HE) and Oil Red O staining. The expression levels of these factors were measured in liver tissues, and TUG1 expression was knocked down to evaluate its functional impact. The results indicate that TUG1 could bind to miR-29a-3p, thereby regulating the expression of HMGCR and SREBP-2. Tug1 expression is upregulated in livers of MAFLD models compared with control groups, showing a negative correlation with miR-29a-3p and a positive correlation with HMGCR and SREBP-2. Furthermore, the knockdown of Tug1 in mouse livers reduced hepatic lipid deposition significantly. In summary, TUG1 could modulate the SREBP-2/HMGCR pathway by binding to miR-29a-3p, thus influencing lipid metabolism. These findings suggest that TUG1 may serve as a potential therapeutic target for MAFLD.