LINC01093 upregulation protects against alcoholic hepatitis through inhibition of NF-κB signaling pathway

Abstract The long noncoding RNAs (lncRNAs) have been proven to be involved in the development of alcoholic hepatitis (AH), which has been regarded as a severe form of acute liver injury with a high mortality rate. Through the GEO database, the differentially expressed LINC01093 and intercellular cell adhesion molecule-1 (ICAM-1) were identified in AH. Then, in order to clarify their specific role and underlying mechanism in AH, we constructed an AH mouse model by using Lieber-Decarli alcoholic feed. It was further found that LINC01093 was poorly-expressed and ICAM-1 was highly-expressed in AH mice. After that, the interactions among LINC01093, ICAM-1, and NF-κB signaling pathway were explored, which verified that LINC01093 could target ICAM-1 and further inhibit the NF-κB signaling pathway. Finally, after the hepatocytes were isolated from the AH mice, the expression of LINC01093 was up- or down-regulated or of ICAM-1 was silenced in order to evaluate their effect on cell viability and apoptosis. The corresponding results demonstrated that after overexpression of LINC01093 or silencing of ICAM-1, the cell viability was increased and cell apoptosis was reduced in the hepatocytes of AH mice. Moreover, the silencing of LINC01093 was observed to inhibit the viability and promote the apoptosis of hepatocytes of AH mice. Taken together, these results provide evidence that overexpression of LINC01093 could effectively suppress hepatocyte apoptosis and promote proliferation by inhibiting the ICAM-1-mediated NF-κB signaling pathway, thus playing a functional role in AH and hepatic fibrosis.