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  • Title: Up regulation of liver-enriched transcription factors HNF4a and HNF6 and liver-specific microRNA (miR-122) by inhibition of let-7b in mesenchymal stem cells.
    Author: Alizadeh E, Akbarzadeh A, Eslaminejad MB, Barzegar A, Hashemzadeh S, Nejati-Koshki K, Zarghami N.
    Journal: Chem Biol Drug Des; 2015 Mar; 85(3):268-79. PubMed ID: 25059576.
    Abstract:
    MicroRNAs are small non-coding RNAs that regulate key processes of the stem cells. Although, microRNAs have emerged as powerful regulators of differentiation, few studies have been focused on the post-transcriptional regulation of hepatic differentiation in mesenchymal stem cells (MSCs) by microRNAs. The aim of this study was to evaluate the specific effect of let-7 microRNAs in particular let-7b in hepatic commitment of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). The dynamic expression profile of let-7a, b, c microRNAs and two liver-enriched transcription factors (LETFs) HNF4a and HNF6 was studied during in vitro hepatic differentiation of hAT-MSCs. Let-7b was used for transient overexpression and knockdown investigations. It was shown that the expression of LETFs is inversely correlated with those of let-7 miRNAs during differentiation progress (p < 0.05). Inhibition of let-7b caused upregulation of LETFs, an increase in the expression of miR-122 (p < 0.01) emulating the features of functional hepatocytes, and accumulation of hAT-MSCs in the G0 /G1 phase of cell cycle, triggering initiation of hepatic commitment. In conclusion, transient inhibition of let-7b activates hepatic differentiation of hAT-MSCs. The findings of this work might help optimization of in vitro hepatogenic differentiation utilizing microRNAs and hAT-MSCs that could be used for therapeutic purposes.
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