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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| Veröffentlicht in: | Biochemical and biophysical research communications 2008-12, Vol.377 (2), p.434-440 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1016/j.bbrc.2008.09.159 |
| format | Article |
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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.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2008.09.159</identifier><identifier>PMID: 18930031</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Biochemical and biophysical research communications, 2008-12, Vol.377 (2), p.434-440</ispartof><rights>2008 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-2e51883c7557cace708965f600998fcf7f3ce78b84f86394b99a97afd68df96f3</citedby><cites>FETCH-LOGICAL-c385t-2e51883c7557cace708965f600998fcf7f3ce78b84f86394b99a97afd68df96f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2008.09.159$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18930031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Nan Sook</creatorcontrib><creatorcontrib>Kim, Jong Soo</creatorcontrib><creatorcontrib>Cho, Wha Ja</creatorcontrib><creatorcontrib>Lee, Man Ryul</creatorcontrib><creatorcontrib>Steiner, Riley</creatorcontrib><creatorcontrib>Gompers, Andrea</creatorcontrib><creatorcontrib>Ling, Daijun</creatorcontrib><creatorcontrib>Zhang, Jae</creatorcontrib><creatorcontrib>Strom, Pl</creatorcontrib><creatorcontrib>Behlke, Mark</creatorcontrib><creatorcontrib>Moon, Sung-Hwan</creatorcontrib><creatorcontrib>Salvaterra, Paul M.</creatorcontrib><creatorcontrib>Jove, Richard</creatorcontrib><creatorcontrib>Kim, Kye-Seong</creatorcontrib><title>miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>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.</description><subject>Cell cycle</subject><subject>Cell Differentiation</subject><subject>Cell Line, Tumor</subject><subject>Cyclin D2</subject><subject>Cyclins - biosynthesis</subject><subject>Cyclins - genetics</subject><subject>Embryonal Carcinoma Stem Cells - cytology</subject><subject>Embryonal Carcinoma Stem Cells - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Human embryonal carcinoma cells</subject><subject>Human embryonic stem cells</subject><subject>Humans</subject><subject>microRNA array</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>MicroRNAs - physiology</subject><subject>miRNA expression</subject><subject>miRNAs</subject><subject>Oct4</subject><subject>Pluripotent Stem Cells - cytology</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>Protein Biosynthesis - genetics</subject><subject>Retinoic acid</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Stemness</subject><subject>Transcriptional Activation</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGKFDEQhoO4uOPqC3iQnLx1W0mm0wl4kXFXhYUFUfAW0ulEM3TSbdK9OCf3QfTl9klMOwPe9BCKFF_9FPUh9IxATYDwl_u665KpKYCoQdakkQ_QhoCEihLYPkQbAOAVleTzOXqc8x6AkC2Xj9A5EZIBMLJBP4L_UDGgHQ7ax7m8jO_vfubZhmhzvr_7hUeHvy5BR2xDlw5j1AM2Ohkfx6CxscOQcXfA05jnak46ZpP8NPs_XLJflkGvnzVldzCDj_gNxfb7lEp66T9BZ04P2T491Qv06ery4-5ddX3z9v3u9XVlmGjmitqGCMFM2zSt0ca2ICRvHAeQUjjjWsdKU3Ri6wRncttJqWWrXc9F7yR37AK9OOZOafy22Dyr4PO6vI52XLLishWUUfpfkEhOGyZFAekRNGnMOVmnpuSDTgdFQK1-1F6tftTqR4FUxU8Zen5KX7pg-78jJyEFeHUEbDnGrbdJZeNtNLb3yZpZ9aP_V_5v-nSlCQ</recordid><startdate>20081212</startdate><enddate>20081212</enddate><creator>Lee, Nan Sook</creator><creator>Kim, Jong Soo</creator><creator>Cho, Wha Ja</creator><creator>Lee, Man Ryul</creator><creator>Steiner, Riley</creator><creator>Gompers, Andrea</creator><creator>Ling, Daijun</creator><creator>Zhang, Jae</creator><creator>Strom, Pl</creator><creator>Behlke, Mark</creator><creator>Moon, Sung-Hwan</creator><creator>Salvaterra, Paul M.</creator><creator>Jove, Richard</creator><creator>Kim, Kye-Seong</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20081212</creationdate><title>miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-2e51883c7557cace708965f600998fcf7f3ce78b84f86394b99a97afd68df96f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Cell cycle</topic><topic>Cell Differentiation</topic><topic>Cell Line, Tumor</topic><topic>Cyclin D2</topic><topic>Cyclins - biosynthesis</topic><topic>Cyclins - genetics</topic><topic>Embryonal Carcinoma Stem Cells - cytology</topic><topic>Embryonal Carcinoma Stem Cells - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Human embryonal carcinoma cells</topic><topic>Human embryonic stem cells</topic><topic>Humans</topic><topic>microRNA array</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>MicroRNAs - physiology</topic><topic>miRNA expression</topic><topic>miRNAs</topic><topic>Oct4</topic><topic>Pluripotent Stem Cells - cytology</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>Protein Biosynthesis - genetics</topic><topic>Retinoic acid</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Stemness</topic><topic>Transcriptional Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Nan Sook</creatorcontrib><creatorcontrib>Kim, Jong Soo</creatorcontrib><creatorcontrib>Cho, Wha Ja</creatorcontrib><creatorcontrib>Lee, Man Ryul</creatorcontrib><creatorcontrib>Steiner, Riley</creatorcontrib><creatorcontrib>Gompers, Andrea</creatorcontrib><creatorcontrib>Ling, Daijun</creatorcontrib><creatorcontrib>Zhang, Jae</creatorcontrib><creatorcontrib>Strom, Pl</creatorcontrib><creatorcontrib>Behlke, Mark</creatorcontrib><creatorcontrib>Moon, Sung-Hwan</creatorcontrib><creatorcontrib>Salvaterra, Paul M.</creatorcontrib><creatorcontrib>Jove, Richard</creatorcontrib><creatorcontrib>Kim, Kye-Seong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Nan Sook</au><au>Kim, Jong Soo</au><au>Cho, Wha Ja</au><au>Lee, Man Ryul</au><au>Steiner, Riley</au><au>Gompers, Andrea</au><au>Ling, Daijun</au><au>Zhang, Jae</au><au>Strom, Pl</au><au>Behlke, Mark</au><au>Moon, Sung-Hwan</au><au>Salvaterra, Paul M.</au><au>Jove, Richard</au><au>Kim, Kye-Seong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2008-12-12</date><risdate>2008</risdate><volume>377</volume><issue>2</issue><spage>434</spage><epage>440</epage><pages>434-440</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18930031</pmid><doi>10.1016/j.bbrc.2008.09.159</doi><tpages>7</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2008-12, Vol.377 (2), p.434-440 |
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| 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 |
| title | miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression |
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