miR-302b maintains "stemness" of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression
- 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
- Issue Date
- Dec-2008
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- miRNAs; miRNA expression; " Stemness" ; microRNA array; Human embryonal carcinoma cells; Human embryonic stem cells; Cyclin D2; Oct4; Cell cycle; Retinoic acid
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.377, no.2, pp.434 - 440
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 377
- Number
- 2
- Start Page
- 434
- End Page
- 440
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/171762
- DOI
- 10.1016/j.bbrc.2008.09.159
- ISSN
- 0006-291X
- 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 clown-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.
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