Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest
miRNAs regulate gene expression by inhibiting translation or by targeting messenger RNA (mRNA) for degradation in a post-transcriptional fashion. In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (...
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| Veröffentlicht in: | FEBS letters 2008-04, Vol.582 (10), p.1564-1568 |
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| creator | Sun, Fang Fu, Hanjiang Liu, Qin Tie, Yi Zhu, Jie Xing, Ruiyun Sun, Zhixian Zheng, Xiaofei |
| description | miRNAs regulate gene expression by inhibiting translation or by targeting messenger RNA (mRNA) for degradation in a post-transcriptional fashion. In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). We also demonstrate that miR-34a targets the 3′-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. In addition, we show that overexpression of miR-34a induces a significant G1 cell-cycle arrest in the A549 cell line. Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically. |
| doi_str_mv | 10.1016/j.febslet.2008.03.057 |
| format | Article |
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In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). We also demonstrate that miR-34a targets the 3′-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. In addition, we show that overexpression of miR-34a induces a significant G1 cell-cycle arrest in the A549 cell line. Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/j.febslet.2008.03.057</identifier><identifier>PMID: 18406353</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>3' Untranslated Regions - genetics ; 3' Untranslated Regions - metabolism ; 3′-untranslated region ; 3′-UTR ; Base Sequence ; CCND1 ; CCND3 ; CCNE2 ; CDK4/6 ; CDK6 ; Cell cycle ; Cell Line, Tumor ; Cyclin D ; cyclin D1 ; cyclin D3 ; cyclin E2 ; cyclin-dependent kinase 4/6 ; Cyclin-Dependent Kinase 6 - genetics ; Cyclins - genetics ; Down-Regulation ; G1 Phase - genetics ; Gene Expression Regulation ; hepatocyte growth factor receptor ; Humans ; messenger RNA ; MET ; MicroRNA ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miR-34a ; miRNA ; mRNA ; Phosphorylation ; Retinoblastoma - genetics ; Retinoblastoma - metabolism</subject><ispartof>FEBS letters, 2008-04, Vol.582 (10), p.1564-1568</ispartof><rights>2008 Federation of European Biochemical Societies</rights><rights>FEBS Letters 582 (2008) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5252-dc057512a5c3dc69aff1255fefb5c85b93ff076042c3b503c5867340f924e0a03</citedby><cites>FETCH-LOGICAL-c5252-dc057512a5c3dc69aff1255fefb5c85b93ff076042c3b503c5867340f924e0a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.febslet.2008.03.057$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.febslet.2008.03.057$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,1418,1434,3551,27926,27927,45576,45577,45997,46411,46835</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18406353$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Fang</creatorcontrib><creatorcontrib>Fu, Hanjiang</creatorcontrib><creatorcontrib>Liu, Qin</creatorcontrib><creatorcontrib>Tie, Yi</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Xing, Ruiyun</creatorcontrib><creatorcontrib>Sun, Zhixian</creatorcontrib><creatorcontrib>Zheng, Xiaofei</creatorcontrib><title>Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>miRNAs regulate gene expression by inhibiting translation or by targeting messenger RNA (mRNA) for degradation in a post-transcriptional fashion. In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). We also demonstrate that miR-34a targets the 3′-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. In addition, we show that overexpression of miR-34a induces a significant G1 cell-cycle arrest in the A549 cell line. Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically.</description><subject>3' Untranslated Regions - genetics</subject><subject>3' Untranslated Regions - metabolism</subject><subject>3′-untranslated region</subject><subject>3′-UTR</subject><subject>Base Sequence</subject><subject>CCND1</subject><subject>CCND3</subject><subject>CCNE2</subject><subject>CDK4/6</subject><subject>CDK6</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cyclin D</subject><subject>cyclin D1</subject><subject>cyclin D3</subject><subject>cyclin E2</subject><subject>cyclin-dependent kinase 4/6</subject><subject>Cyclin-Dependent Kinase 6 - genetics</subject><subject>Cyclins - genetics</subject><subject>Down-Regulation</subject><subject>G1 Phase - genetics</subject><subject>Gene Expression Regulation</subject><subject>hepatocyte growth factor receptor</subject><subject>Humans</subject><subject>messenger RNA</subject><subject>MET</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miR-34a</subject><subject>miRNA</subject><subject>mRNA</subject><subject>Phosphorylation</subject><subject>Retinoblastoma - genetics</subject><subject>Retinoblastoma - metabolism</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS0EokvhI4B84pYwtmPHOSHIbv-oFZUKnC3HGSOvskmxN6322-NoV-qxnEYj_ebNmzeEfGRQMmDqy7b02KUB9yUH0CWIEmT9iqyYrkUhKqVfkxUAqwpZN-KMvEtpC7nXrHlLzpiuQAkpVmSznp7GiH_mwe7DNNLJ07b9sWbUjj1t1zeKdge6C_dZ0tIw9rPDRB0OA3UHNyC1MWLavydvvB0SfjjVc_L7YvOrvSpu7y6v22-3hZNc8qJ32aNk3Eoneqca6z3jUnr0nXRado3wHmoFFXeikyCc1KoWFfiGVwgWxDn5fNR9iNPfOS82u5AWN3bEaU5GNQzqulIvgqzRWgNrMiiPoItTShG9eYhhZ-PBMDBL0GZrTkGbJWgDwuQj8tyn04K522H_PHVKNgNXR-ApDHj4P1VzsfnOfy5fW54GGkCA4lnq61EKc7SPAaNJLuDosA8R3d70U3jB7T9YgKPh</recordid><startdate>20080430</startdate><enddate>20080430</enddate><creator>Sun, Fang</creator><creator>Fu, Hanjiang</creator><creator>Liu, Qin</creator><creator>Tie, Yi</creator><creator>Zhu, Jie</creator><creator>Xing, Ruiyun</creator><creator>Sun, Zhixian</creator><creator>Zheng, Xiaofei</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20080430</creationdate><title>Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest</title><author>Sun, Fang ; Fu, Hanjiang ; Liu, Qin ; Tie, Yi ; Zhu, Jie ; Xing, Ruiyun ; Sun, Zhixian ; Zheng, Xiaofei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5252-dc057512a5c3dc69aff1255fefb5c85b93ff076042c3b503c5867340f924e0a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>3' Untranslated Regions - genetics</topic><topic>3' Untranslated Regions - metabolism</topic><topic>3′-untranslated region</topic><topic>3′-UTR</topic><topic>Base Sequence</topic><topic>CCND1</topic><topic>CCND3</topic><topic>CCNE2</topic><topic>CDK4/6</topic><topic>CDK6</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cyclin D</topic><topic>cyclin D1</topic><topic>cyclin D3</topic><topic>cyclin E2</topic><topic>cyclin-dependent kinase 4/6</topic><topic>Cyclin-Dependent Kinase 6 - genetics</topic><topic>Cyclins - genetics</topic><topic>Down-Regulation</topic><topic>G1 Phase - genetics</topic><topic>Gene Expression Regulation</topic><topic>hepatocyte growth factor receptor</topic><topic>Humans</topic><topic>messenger RNA</topic><topic>MET</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miR-34a</topic><topic>miRNA</topic><topic>mRNA</topic><topic>Phosphorylation</topic><topic>Retinoblastoma - genetics</topic><topic>Retinoblastoma - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Fang</creatorcontrib><creatorcontrib>Fu, Hanjiang</creatorcontrib><creatorcontrib>Liu, Qin</creatorcontrib><creatorcontrib>Tie, Yi</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Xing, Ruiyun</creatorcontrib><creatorcontrib>Sun, Zhixian</creatorcontrib><creatorcontrib>Zheng, Xiaofei</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</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>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Fang</au><au>Fu, Hanjiang</au><au>Liu, Qin</au><au>Tie, Yi</au><au>Zhu, Jie</au><au>Xing, Ruiyun</au><au>Sun, Zhixian</au><au>Zheng, Xiaofei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2008-04-30</date><risdate>2008</risdate><volume>582</volume><issue>10</issue><spage>1564</spage><epage>1568</epage><pages>1564-1568</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>miRNAs regulate gene expression by inhibiting translation or by targeting messenger RNA (mRNA) for degradation in a post-transcriptional fashion. In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). We also demonstrate that miR-34a targets the 3′-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. In addition, we show that overexpression of miR-34a induces a significant G1 cell-cycle arrest in the A549 cell line. Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>18406353</pmid><doi>10.1016/j.febslet.2008.03.057</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3' Untranslated Regions - genetics 3' Untranslated Regions - metabolism 3′-untranslated region 3′-UTR Base Sequence CCND1 CCND3 CCNE2 CDK4/6 CDK6 Cell cycle Cell Line, Tumor Cyclin D cyclin D1 cyclin D3 cyclin E2 cyclin-dependent kinase 4/6 Cyclin-Dependent Kinase 6 - genetics Cyclins - genetics Down-Regulation G1 Phase - genetics Gene Expression Regulation hepatocyte growth factor receptor Humans messenger RNA MET MicroRNA MicroRNAs - genetics MicroRNAs - metabolism miR-34a miRNA mRNA Phosphorylation Retinoblastoma - genetics Retinoblastoma - metabolism |
| title | Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest |
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