Upregulation of MiR‐122 via Trichostatin A Treatments in Hepatocyte‐like Cells Derived from Mesenchymal Stem Cells

Abstract

The miR-122 is a tissue-specific miRNA; its expression is abundant in liver. MiR-122 upregulation is crucial for differentiation, functionality, and maintenance of differentiated phenotype in hepatocytes. The improving effects of trichostatin A (TSA) on hepatic differentiation have been reported previously. The aim of this study was to determine whether TSA can affect the expression of miR-122 in hepatocyte-like cells (HLCs) generated from human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). The hepatic differentiation of hAT-MSCs induced by a mixture of growth factors and cytokines either with or without TSA treatments. The functionality of HLCs generated with or without TSA and the expression levels of miR-122 were studied. The expression levels of miR-122 in TSA-treated HLCs was significantly (p < 0.05) higher than those generated by growth factors and cytokines, only. The downregulation of a-fetoprotein (AFP) levels but enhanced albumin synthesis (p < 0.05) and upregulation of liver-enriched transcription factors (LETFs) HNF4α (hepatocyte nuclear factor 4α) and HNF6 (hepatocyte nuclear factor 6) were observed in TSA-treated HLCs (p < 0.05). In conclusion, administration of TSA in hepatogenic differentiation of hAT-MSCs resulted in higher expression levels of miR-122, facilitation of differentiation, and subsequently attenuation of AFP levels.

Comparison of genome‐wide analysis techniques to DNA methylation analysis in human cancer

“…DNA methylation as an epigenetic alteration commonly occurs at 5′cytosine (5′C) of pyrimidine cycle and plays a key role in genome regulation and development (Bird, ; Holliday & Pugh, ; Momparler & Bovenzi, ). Apart from its role in physiological functions, aberrant DNA methylation is related to the inappropriate transcriptional silencing of genes (Issa, ; Molavi et al, ), that provides an advantage for several diseases such as diabetes, heart disease, autoimmune, and aging‐related diseases (Egger, Liang, Aparicio, & Jones, ; Irier & Jin, ; Jayaraman, ; Movassagh, Vujic, & Foo, ; Robertson, ) and many types of cancer including colorectal (Hughes et al, ; Samowitz, ; Toyota et al, ), lung (Marsit et al, ; Shigematsu et al, ), liver (Alizadeh et al, ; Shen et al, ), and breast cancer (Fang et al, ). In contrast to normal cells, cancer cells globally exhibit a lower levels of 5‐methylcytosine in the genome, but simultaneously a higher levels of methylation in tumor suppressor genes promoters (Jones & Baylin, , ).…”

Efficient programming of human mesenchymal stem cell‐derived hepatocytes by epigenetic regulations

“…44,45 miR-122 is a well-studied microRNA playing an important role in regulating hepatocyte development and differentiation 46 ; a very recent study found that TSA administration during hepatogenic differentiation of hMSCs resulted in higher expression levels of miR-122 facilitating reprogramming efficiency providing a potential underlying molecular regulatory cue of hMSC-to-liver differentiation. 47 A previous study has shown that miR-122 expression is essential for HCV proliferation in host cells after infection. 48 Mechanistically, several reports revealed that a specific interaction between the seed domain of miR-122 and the complementary sequences in the 5′UTR of HCV RNA is essential for the enhancement of translation and replication of the HCV genome.…”

“…HCV infection is a multi‐step event, and it was shown that liver‐specific microRNA miR‐122 is essential for HCV replication . miR‐122 is a well‐studied microRNA playing an important role in regulating hepatocyte development and differentiation; a very recent study found that TSA administration during hepatogenic differentiation of hMSCs resulted in higher expression levels of miR‐122 facilitating reprogramming efficiency providing a potential underlying molecular regulatory cue of hMSC‐to‐liver differentiation . A previous study has shown that miR‐122 expression is essential for HCV proliferation in host cells after infection .…”

Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells

“…There have been many studies of the effects of histone deacetylase inhibitors (HDACis), such as trichostatin A and dimethylsulphoxide, on hepatocyte differentiation. 78–84 HDACis have a broad range of effects, including up-regulating expression of LETFs, such as HNF4A, HNF1A, CEBPA, and FOXA2, 79 and increasing transcriptional activity by binding to promoter regions of CYP genes and glucose-6-phosphate dehydrogenase. 80–82 Additionally, HDAC is regulate liverspecific expression of MIR122.…”