LncRNA TINCR/miR-31-5p/C/EBP-α feedback loop modulates the adipogenic differentiation process in human adipose tissue-derived mesenchymal stem cells

Abstract

The adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs) is a critical issue in many obesity-related disorders and it can be regulated by a crucial transcription factor, CCAAT enhancer binding protein α (C/EBP-α). Apart from, the involvement of non-coding RNAs in adipogenic differentiation has also been reported. As we know, Terminal differentiation-induced ncRNA (TINCR) is required in somatic tissue differentiation. Recently, we found that TINCR could modulate adipogenic differentiation in hADSCs. As predicted by JASPAR and further confirmed by luciferase reporter gene and ChIP assays, C/EBP-α could bind to the promoter region of lncRNA TINCR to activate its expression. Further, miR-31 was confirmed as a direct target of TINCR and could be negatively regulated by TINCR via competing endogenous RNA (ceRNA) mechanism; miR-31 inhibition enhanced the adipogenic differentiation in hADSCs. More importantly, we found that miR-31 directly bound to the 3′-UTR of C/EBP-α to inhibit its expression. Taken together, in hADSCs, lncRNA TINCR, miR-31 and C/EBP-α formed a feedback loop to modulate the adipogenic differentiation process. From the perspective of lncRNA-miRNA-mRNA regulation, we provided a novel regulatory mechanism of hADSCs adipogenic differentiation. Keywords: Human adipose tissue-derived mesenchymal stem cells (hADSCs), Adipogenic differentiation, lncRNA TINCR, miR-31, C/EBP-α