LncRNA HCG11 inhibits adipocyte differentiation in human adipose-derived mesenchymal stem cells by sponging miR-204-5p to upregulate SIRT1

Background: LncRNAs have been discovered to play a key role in adipogenesis, vital in regulating adipose developmen t. Numerous evidences show that adipogenesis is the leading cause of obesity, while the role of lncRNA HLA complex group 11 ( HCG11 ) in adipocyte differentiation has not been elucidated. Methods: hAdMSCs were used to establish a model of cell differentiation in vitro . Expression of lncRNA HCG11 was detected by RT-qPCR analysis. Transfection of the shRNA targeting HCG11 or pcDNA-HCG11 into hAdMSCs was also assessed. The adipogenic marker proteins C/EBPα, FABP4 and PPARγ2 and important inflammatory factors IL-6 and TNF-α were detected by Western blot. Bioinformatics analysis predicted the target genes of HCG11 and mir-204-5p, which was confirmed by luciferase reporter gene analysis and RNA pull-down analysis. Results: Here we show that lncRNA HCG11 was decreased as the degree of adipogenesis. The expression of C/EBPα, FABP4 and PPARγ2 were significantly downregulated transfected with pcDNA-HCG11 in hAdMSCs at different stages, while knockdown lncRNA HCG11 can promote adipocyte differentiation. In addition, miR-204-5p was a potential target gene of HCG11 and SIRT1 could directly target miR-204-5p. Overexpression of SIRT1 or transfected with agonists of SIRT1 (Res) significantly inhibited adipogenic marker protein levels and inflammatory responses, and the proliferation of hAdMSCs were also inhibited. pcDNA-HCG11 and miR-204-5p mimic were co-transfected into hAdMSCs, we found that miR-204-5p mimic reversed the suppressor effect of pcDNA-HCG11. Conclusion: Our findings showed that HCG11 negatively regulated cell proliferation, inflammatory responses and adipogenesis by miR-204-5p/SIRT1 axis. And our findings may provide a new target for the study of adipogenesis in hAdMSCs and obesity.