miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression

Embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) possess the remarkable property of self-renewal and differentiation potency. They are model preparations for investigating the underlying mechanisms of “stemness”. microRNAs are recently discovered small noncoding RNAs with a broad spe...

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Published in:	Biochemical and biophysical research communications 2008-12, Vol.377 (2), p.434-440
Main Authors:	Lee, Nan Sook, Kim, Jong Soo, Cho, Wha Ja, Lee, Man Ryul, Steiner, Riley, Gompers, Andrea, Ling, Daijun, Zhang, Jae, Strom, Pl, Behlke, Mark, Moon, Sung-Hwan, Salvaterra, Paul M., Jove, Richard, Kim, Kye-Seong
Format:	Article
Language:	eng
Subjects:	Cell cycle Cell Differentiation Cell Line, Tumor Cyclin D2 Cyclins - biosynthesis Cyclins - genetics Embryonal Carcinoma Stem Cells - cytology Embryonal Carcinoma Stem Cells - metabolism Gene Expression Regulation Human embryonal carcinoma cells Human embryonic stem cells Humans microRNA array MicroRNAs - genetics MicroRNAs - metabolism MicroRNAs - physiology miRNA expression miRNAs Oct4 Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism Protein Biosynthesis - genetics Retinoic acid RNA, Messenger - biosynthesis Stemness Transcriptional Activation
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Summary:	Embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) possess the remarkable property of self-renewal and differentiation potency. They are model preparations for investigating the underlying mechanisms of “stemness”. microRNAs are recently discovered small noncoding RNAs with a broad spectrum of functions, especially in control of development. Here, we show that miR-302b indirectly regulates expression of the pluripotent stem cell marker Oct4, and it directly regulates expression of Cyclin D2 protein, a developmental regulator during gastrulation. Using loss-of function and gain-of function approaches, we demonstrate that functional miR-302b is necessary to maintain stem cell self-renewal and inhibit neuronal differentiation of human ECCs. During retinoic acid-induced neuronal differentiation, Cyclin D2 protein but not mRNA expression is strongly increased, concurrent with the down-regulation of miR-302b and Oct4. Our results suggest that miR-302b plays an important role in maintaining the pluripotency of ECCs and probably ESCs, by post-transcriptional regulation of Cyclin D2 expression.
ISSN:	0006-291X 1090-2104