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

Hepatitis is a major public health problem that increases the risk of liver cirrhosis and liver cancer. Numerous studies have revealed that long non-coding RNAs (lncRNAs) exert essential function in the inflammatory response of multiple organs. Herein, we aimed to explore the effect of lncRNA TUG1 in LPS-induced hepatocyte inflammation response and further illuminate the underlying mechanisms. Mice were intraperitoneally injected with LPS, and the liver inflammation was evaluated. Microarray showed that lncRNA TUG1 was upregulated in LPS-induced hepatocyte inflammation. qRT-PCR and immunofluorescence assay indicated a significant increase of TUG1 in mice with LPS injection. Functional analysis showed that si-TUG1 inhibited LPS-induced inflammation response in mice liver, inhibited apoptosis level, and protected liver function. Then, we knock down TUG1 in normal human hepatocyte AML12. Consistent with in vivo results, si-TUG1 removed the injury of LPS on AML12 cells. Furthermore, TUG1 acted as a sponge of miR-140, and miR-140 directly targeted TNFα (TNF). MiR-140 or si-TNF remitted the beneficial effects of TUG1 on LPS-induced hepatocyte inflammation response both in vitro and in vivo. Our data revealed that deletion of TUG1 protected against LPS-induced hepatocyte inflammation via regulating miR-140/TNF, which might provide new insight for hepatitis treatment.