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Gene. 2016 Oct 10;591(1):48-57. doi: 10.1016/j.gene.2016.06.047. Epub 2016 Jun 23.

miR-145 modulates lncRNA-ROR and Sox2 expression to maintain human amniotic epithelial stem cell pluripotency and β islet-like cell differentiation efficiency.

Author information

1
Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China.
2
Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China; Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: te.liu@yale.edu.
3
Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
4
Laboratoire PROTEE, Bâtiment R, Université du Sud Toulon-Var, 83957, La Garde Cedex, France.
5
Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200040, China.
6
Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China. Electronic address: tduan@yahoo.com.

Abstract

In this study, we observed a great reduction in the expression of the endogenous long noncoding RNA ROR (lncRNA-ROR) and the stem cell transcription factor Sox2, in contrast to a marked increase in miR-145 expression, during the course of in vitro induced differentiation of human amniotic epithelial stem cells (HuAECs). Bioinformatics analysis and the luciferase reporter assay revealed binding of miR-145 to specific sites in lncRNA-ROR and Sox2, silencing their expression. Overexpression of a lncRNA-ROR-specific siRNA effectively downregulated the expression levels of Sox2 and other stem cell markers in HuAECs while weakening the efficiency of HuAEC differentiation into β islet-like cells. Moreover, the in vitro response of HuAEC-derived β islet-like cells to extracellular stimuli and C-peptide release by these cells were markedly weakened in the siRNA-ROR transfection group. Furthermore, the in vivo expression of β islet-like cell biomarkers was substantially reduced in HuAECs in the siRNA-ROR transfection group, and their in vivo β islet-like cell differentiation and insulin release capacities were reduced in a streptozocin-induced diabetic rat model. The experimental results indicate that lncRNA-ROR effectively maintains Sox2 gene expression through competitive binding to miR-145, achieving pluripotency maintenance in HuAECs and regulation of their directed β islet-like cell differentiation efficiency.

KEYWORDS:

Human amniotic epithelial stem cell; Long noncoding RNA ROR; MicroRNA-145; Sox2; β Islet-like cell

PMID:
27346547
DOI:
10.1016/j.gene.2016.06.047
[Indexed for MEDLINE]
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