Construction and comprehensive analysis of a lncRNA-mRNA interactive network to reveal a potential lncRNA for hepatic encephalopathy development.

Abstract

Little is known about the role of lncRNA-mRNA regulatory relationships in hepatic encephalopathy (HE). Here, we aimed to construct the potential lncRNA and mRNA interactive network in forecasting HE development in patients with liver cirrhosis using different bioinformatic analysis method. Through analyses, we found that AL137857.1 had the most connections with other mRNAs and was deemed as a hub lncRNA. It was obviously upregulated in HE patients, which was also validated by another independent dataset. GO and KEGG analyses suggested that AL137857.1 was involved in microglial cell activation, phagocytosis, cytokine biosynthetic process, interleukin-6 production and tumor necrosis factor production. In vitro experiments suggested LPS could stimulate microglia to generate AL137857.1. In addition, we found that inhibition of AL137857.1 suppressed the expression of a series of inflammatory cytokines, including IL-1, IL-6, TNF-α, Cox2 and iNOS. Conversely, AL137857.1 over-expression induced a marked increase in these factors. Finally, AL137857.1 was demonstrated to be highly associated with the ability of microglial phagocytosis. Taken together, we have constructed a lncRNA-mRNA regulatory network associated with HE and explored the biological significance of mRNAs in the network, then discovered a novel lncRNA AL137857.1 in HE that might act as a potential regulator of the downstream inflammatory cytokines.