Downregulation of IL6 Targeted MiR-376b May Contribute to a Positive IL6 Feedback Loop During Early Liver Regeneration in Mice.

MicroRNAs (miRNAs) are a group of endogenous, small, noncoding RNAs implicated in a variety of biological processes, including cell proliferation, apoptosis, differentiation and metabolism. The present study aims to explore the potential role and molecular mechanism of miR-376b during the early phase of liver regeneration.,MiRNA profiling microarrays were used to assess the changes in miRNA expression. For functional analysis, cell proliferation, apoptosis assays, real time quantitative PCR and westernblot analysis were performed.,The comprehensive miRNA expression profiling assays on regenerating liver tissues 4 h after partial hepatectomy (PH) showed that three miRNAs (miR-127, miR-376b and miR-494) located in the Dlk1-Gtl2 miRNA cluster were significantly downregulated. In vitro functional studies demonstrated that high-level interleukin 6 (IL6) inhibited the expression of miR-376b, and miR-376b mimics treatment decreased cell proliferation and increased apoptosis. Further target analysis showed that miR-376b reduced the mRNA and protein expression levels of NF-kappa-B inhibitor zeta (NFKBIZ) and signal transducers and transcription activators 3 (STAT3). Additionally, IL6-induced miR-376b downregulation would, in turn, increase the expression of IL-6 possibly via a feedback loop involving NFKBIZ or/and STAT3.,During the early phase of liver regeneration, miR-376b expression was significantly decreased. Our findings reveal that a regulatory circuitry between miR-376b and IL-6 may exist, which trigger the initiation of liver regeneration.