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Article: MYC protein inhibits transcription of the MicroRNA cluster MC-let-7a-1∼let-7d via noncanonical E-box
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TitleMYC protein inhibits transcription of the MicroRNA cluster MC-let-7a-1∼let-7d via noncanonical E-box
 
AuthorsWang, Z3
Lin, S5 3
Li, JJ5
Xu, Z5
Yao, H4
Zhu, X2
Xie, D3
Shen, Z1
Sze, J5
Li, K3
Lu, G5
Chan, DTM5
Poon, WS5
Kung, HF5 3
Lin, MCM5
 
Issue Date2011
 
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
CitationJournal Of Biological Chemistry, 2011, v. 286 n. 46, p. 39703-39714 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M111.293126
 
AbstractThe human microRNA cluster MC-let-7a-1∼let-7d, with three members let-7a-1, let-7f-1, and let-7d, is an important cluster of the let-7 family. These microRNAs play critical roles in regulating development and carcinogenesis. Therefore, precise control of MC-let-7a-1∼let-7d level is critical for cellular functions. In this study, we first showed that the expression of these three members was significantly reduced in human hepatocellular carcinoma HepG2 cells as compared with the immortalizedhumanliver L02 cells.Wedemonstrated that the MC-let- 7a-1∼let-7d cluster was encoded by a single polycistronic transcript driven by a 10-kb upstream promoter, with two MYC-binding sites. Importantly, MYC inhibited MC-let-7a-1∼let-7d promoter activity via binding to the noncanonical E-box 3 downstream of the transcription start sites, whereas it enhanced promoter activity by binding to the canonical E-box 2 upstream of the transcription start sites. We found that although the binding affinity of MYC to E-box 2 was stronger than E-box 3, the binding quantum of MYC to E-box 3 was significantly higher in cancerous HepG2 cells as compared with the noncancerous L02 cells. In addition, forced expression of let-7 could reverse the MYC-mediated cell proliferation. These findings suggested that in L02 cells with a low level of MYC, MYC binds mainly to E-box 2 to enhance MC-let-7a-1∼let-7d expression. However, in HepG2 cells with an elevated MYC, the extra MYC could bind to E-box 3 to suppress the transcription of MC-let-7a-1∼let-7d and thus enable HepG2 cells to maintain a high level of MYC and a low level of let-7 microRNAs simultaneously. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
 
ISSN0021-9258
2013 Impact Factor: 4.600
 
DOIhttp://dx.doi.org/10.1074/jbc.M111.293126
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWang, Z
 
dc.contributor.authorLin, S
 
dc.contributor.authorLi, JJ
 
dc.contributor.authorXu, Z
 
dc.contributor.authorYao, H
 
dc.contributor.authorZhu, X
 
dc.contributor.authorXie, D
 
dc.contributor.authorShen, Z
 
dc.contributor.authorSze, J
 
dc.contributor.authorLi, K
 
dc.contributor.authorLu, G
 
dc.contributor.authorChan, DTM
 
dc.contributor.authorPoon, WS
 
dc.contributor.authorKung, HF
 
dc.contributor.authorLin, MCM
 
dc.date.accessioned2012-10-08T03:21:10Z
 
dc.date.available2012-10-08T03:21:10Z
 
dc.date.issued2011
 
dc.description.abstractThe human microRNA cluster MC-let-7a-1∼let-7d, with three members let-7a-1, let-7f-1, and let-7d, is an important cluster of the let-7 family. These microRNAs play critical roles in regulating development and carcinogenesis. Therefore, precise control of MC-let-7a-1∼let-7d level is critical for cellular functions. In this study, we first showed that the expression of these three members was significantly reduced in human hepatocellular carcinoma HepG2 cells as compared with the immortalizedhumanliver L02 cells.Wedemonstrated that the MC-let- 7a-1∼let-7d cluster was encoded by a single polycistronic transcript driven by a 10-kb upstream promoter, with two MYC-binding sites. Importantly, MYC inhibited MC-let-7a-1∼let-7d promoter activity via binding to the noncanonical E-box 3 downstream of the transcription start sites, whereas it enhanced promoter activity by binding to the canonical E-box 2 upstream of the transcription start sites. We found that although the binding affinity of MYC to E-box 2 was stronger than E-box 3, the binding quantum of MYC to E-box 3 was significantly higher in cancerous HepG2 cells as compared with the noncancerous L02 cells. In addition, forced expression of let-7 could reverse the MYC-mediated cell proliferation. These findings suggested that in L02 cells with a low level of MYC, MYC binds mainly to E-box 2 to enhance MC-let-7a-1∼let-7d expression. However, in HepG2 cells with an elevated MYC, the extra MYC could bind to E-box 3 to suppress the transcription of MC-let-7a-1∼let-7d and thus enable HepG2 cells to maintain a high level of MYC and a low level of let-7 microRNAs simultaneously. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
 
dc.description.natureLink_to_OA_fulltext
 
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 46, p. 39703-39714 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M111.293126
 
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M111.293126
 
dc.identifier.epage39714
 
dc.identifier.issn0021-9258
2013 Impact Factor: 4.600
 
dc.identifier.issue46
 
dc.identifier.pmid21903590
 
dc.identifier.scopuseid_2-s2.0-81155123696
 
dc.identifier.spage39703
 
dc.identifier.urihttp://hdl.handle.net/10722/168586
 
dc.identifier.volume286
 
dc.languageeng
 
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Biological Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshHek293 Cells
 
dc.subject.meshHep G2 Cells
 
dc.subject.meshHumans
 
dc.subject.meshMicrornas - Biosynthesis - Genetics
 
dc.subject.meshMultigene Family
 
dc.subject.meshProto-Oncogene Proteins C-Myc - Genetics - Metabolism
 
dc.subject.meshResponse Elements
 
dc.subject.meshTranscription, Genetic
 
dc.titleMYC protein inhibits transcription of the MicroRNA cluster MC-let-7a-1∼let-7d via noncanonical E-box
 
dc.typeArticle
 
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<contributor.author>Yao, H</contributor.author>
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<contributor.author>Xie, D</contributor.author>
<contributor.author>Shen, Z</contributor.author>
<contributor.author>Sze, J</contributor.author>
<contributor.author>Li, K</contributor.author>
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<description.abstract>The human microRNA cluster MC-let-7a-1&#8764;let-7d, with three members let-7a-1, let-7f-1, and let-7d, is an important cluster of the let-7 family. These microRNAs play critical roles in regulating development and carcinogenesis. Therefore, precise control of MC-let-7a-1&#8764;let-7d level is critical for cellular functions. In this study, we first showed that the expression of these three members was significantly reduced in human hepatocellular carcinoma HepG2 cells as compared with the immortalizedhumanliver L02 cells.Wedemonstrated that the MC-let- 7a-1&#8764;let-7d cluster was encoded by a single polycistronic transcript driven by a 10-kb upstream promoter, with two MYC-binding sites. Importantly, MYC inhibited MC-let-7a-1&#8764;let-7d promoter activity via binding to the noncanonical E-box 3 downstream of the transcription start sites, whereas it enhanced promoter activity by binding to the canonical E-box 2 upstream of the transcription start sites. We found that although the binding affinity of MYC to E-box 2 was stronger than E-box 3, the binding quantum of MYC to E-box 3 was significantly higher in cancerous HepG2 cells as compared with the noncancerous L02 cells. In addition, forced expression of let-7 could reverse the MYC-mediated cell proliferation. These findings suggested that in L02 cells with a low level of MYC, MYC binds mainly to E-box 2 to enhance MC-let-7a-1&#8764;let-7d expression. However, in HepG2 cells with an elevated MYC, the extra MYC could bind to E-box 3 to suppress the transcription of MC-let-7a-1&#8764;let-7d and thus enable HepG2 cells to maintain a high level of MYC and a low level of let-7 microRNAs simultaneously. &#169; 2011 by The American Society for Biochemistry and Molecular Biology, Inc.</description.abstract>
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Author Affiliations
  1. Shanghai Jiaotong University
  2. Guangdong Medical College
  3. Sun Yat-Sen University
  4. Kunming Medical University
  5. Chinese University of Hong Kong