Silencing lncRNA TUG1 Alleviates LPS-Induced Mouse Hepatocyte Inflammation by Targeting miR-140/TNF

Area of Science:

• Hepatology
• Molecular Biology
• Immunology

Background:

• Hepatitis poses significant public health risks, increasing the incidence of liver cirrhosis and cancer.
• Long non-coding RNAs (lncRNAs) play crucial roles in organ inflammation.
• The specific role of lncRNA TUG1 in LPS-induced hepatocyte inflammation requires elucidation.

Purpose of the Study:

• To investigate the role of lncRNA TUG1 in lipopolysaccharide (LPS)-induced hepatocyte inflammation.
• To explore the underlying molecular mechanisms involving lncRNA TUG1 in liver inflammation.
• To assess the therapeutic potential of targeting lncRNA TUG1 for hepatitis treatment.

Main Methods:

• Mice were injected with LPS to induce liver inflammation.
• Microarray, qRT-PCR, and immunofluorescence assays were used to measure TUG1 expression.
• Functional assays involved TUG1 knockdown in vivo and in vitro (AML12 cells).
• RNA immunoprecipitation and dual-luciferase reporter assays were employed to confirm interactions.

Main Results:

• LPS injection significantly upregulated lncRNA TUG1 expression in mouse liver.
• TUG1 knockdown inhibited LPS-induced inflammation, reduced apoptosis, and protected liver function in vivo and in vitro.
• TUG1 functioned as a molecular sponge for miR-140, which directly targets TNFα.
• Restoring miR-140 or inhibiting TNFα partially reversed the protective effects of TUG1 knockdown.

Conclusions:

• lncRNA TUG1 promotes LPS-induced hepatocyte inflammation via the miR-140/TNFα axis.
• Targeting lncRNA TUG1 may offer a novel therapeutic strategy for hepatitis.
• Understanding the lncRNA TUG1/miR-140/TNFα pathway provides new insights into hepatitis pathogenesis.