1. miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression
- Author
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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, and Kim, Kye-Seong
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CANCER cells , *EMBRYONIC stem cells , *CELL differentiation , *MESSENGER RNA , *GASTRULATION , *CELL cycle - Abstract
Abstract: 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. [Copyright &y& Elsevier]
- Published
- 2008
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