CCAAT/enhancer-binding protein β regulates interleukin-6-induced transmembrane and ubiquitin-like domain containing 1 gene expression in hepatocytes

Abstract

Transmembrane and ubiquitin-like domain containing 1 (Tmub1) protein has a negative effect on liver regeneration; however, the mechanisms of Tmub1 expression regulation are currently unknown. CCAAT/enhancer-binding protein β (C/EBPβ) is a key transcription factor associated with interleukin-6 (IL-6) in liver regeneration. The present study aimed to investigate the involvement of C/EBPβ in the IL-6-induced upregulation of Tmub1. A series of Tmub1 luciferase reporter vectors were constructed to detect the effects of IL-6 on the transcriptional activity of Tmub1. Small interfering RNA and overexpression vectors were employed to either inhibit or enhance the expression of C/EBPβ, respectively, to determine the effect of C/EBPβ on Tmub1 expression in liver cells. Additionally, chromatin immunoprecipitation experiments were performed to determine whether C/EBPβ bound to the Tmub1 gene, and the sequences associated with the regulation of Tmub1 expression by C/EBPβ were subsequently determined. Several potential binding sites of C/EBPβ were identified in the 5′-upstream region of the Tmub1 gene. C/EBPβ expression was positively correlated with Tmub1 gene expression in rat liver cells. Furthermore, it was demonstrated that C/EBPβ bound to 5′-upstream sequences of the Tmub1 gene to enhance the promoter activity. The present study demonstrated that C/EBPβ is a key transcription factor, which can positively regulate the expression of Tmub1 during liver cell proliferation through a possible association with IL-6.