File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Epigenetic silencing of MIR203 in multiple myeloma
  • Basic View
  • Metadata View
  • XML View
TitleEpigenetic silencing of MIR203 in multiple myeloma
 
AuthorsWong, KY2
Liang, R2
So, CC2
Jin, DY2
Costello, JF1
Chim, CS2
 
KeywordsHypermethylation
MicroRNA
MIR203
Myeloma
Tumour suppressor
 
Issue Date2011
 
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH
 
CitationBritish Journal Of Haematology, 2011, v. 154 n. 5, p. 569-578 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1365-2141.2011.08782.x
 
AbstractEpigenetic inactivation of tumour suppressor microRNAs has been implicated in carcinogenesis. We studied the promoter methylation of MIR203 in eight normal marrow controls, eight multiple myeloma (MM) cell lines, 20 monoclonal gammopathy of undetermined significance (MGUS), 123 diagnostic MM and 19 relapsed MM samples by methylation-specific polymerase chain reaction. Promoter of MIR203 was unmethylated in normal controls but homozygously methylated in 25% MM cell lines. Treatment with 5-Aza-2'-deoxycytidine led to promoter demethylation and MIR203 re-expression. Cyclic AMP responsive element binding protein 1 (CREB1) mRNA was predicted as a MIR203 direct target. Luciferase activity was reduced in constructs carrying wild-type CREB1 3'UTR upon MIR203 expression but not in those carrying mutant CREB1 3'UTR. Moreover, restoration of MIR203 led to downregulation of CREB1 protein and inhibition of myeloma cell proliferation. In primary samples, MIR203 methylation occurred in 25.0% MGUS, 23.6% diagnostic MM, and 21.1% relapsed MM samples. In conclusion, MIR203 methylation is disease-specific with reversible gene silencing in MM. MIR203 is a tumour suppressor microRNA inhibiting cellular proliferation by targeting CREB1 mRNA in MM. Comparable occurrence of MIR203 methylation in MGUS and MM at diagnosis or relapse suggested that MIR203 methylation may be an early event in myelomagenesis instead of being acquired during disease progression. © 2011 Blackwell Publishing Ltd.
 
ISSN0007-1048
2013 Impact Factor: 4.959
 
DOIhttp://dx.doi.org/10.1111/j.1365-2141.2011.08782.x
 
ISI Accession Number IDWOS:000294584000004
Funding AgencyGrant Number
Hong Kong Research Grants Council763409M
Funding Information:

This work was supported by the Hong Kong Research Grants Council General Research Fund (Ref. 763409M) awarded to Dr C.S. Chim.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWong, KY
 
dc.contributor.authorLiang, R
 
dc.contributor.authorSo, CC
 
dc.contributor.authorJin, DY
 
dc.contributor.authorCostello, JF
 
dc.contributor.authorChim, CS
 
dc.date.accessioned2011-08-26T14:23:58Z
 
dc.date.available2011-08-26T14:23:58Z
 
dc.date.issued2011
 
dc.description.abstractEpigenetic inactivation of tumour suppressor microRNAs has been implicated in carcinogenesis. We studied the promoter methylation of MIR203 in eight normal marrow controls, eight multiple myeloma (MM) cell lines, 20 monoclonal gammopathy of undetermined significance (MGUS), 123 diagnostic MM and 19 relapsed MM samples by methylation-specific polymerase chain reaction. Promoter of MIR203 was unmethylated in normal controls but homozygously methylated in 25% MM cell lines. Treatment with 5-Aza-2'-deoxycytidine led to promoter demethylation and MIR203 re-expression. Cyclic AMP responsive element binding protein 1 (CREB1) mRNA was predicted as a MIR203 direct target. Luciferase activity was reduced in constructs carrying wild-type CREB1 3'UTR upon MIR203 expression but not in those carrying mutant CREB1 3'UTR. Moreover, restoration of MIR203 led to downregulation of CREB1 protein and inhibition of myeloma cell proliferation. In primary samples, MIR203 methylation occurred in 25.0% MGUS, 23.6% diagnostic MM, and 21.1% relapsed MM samples. In conclusion, MIR203 methylation is disease-specific with reversible gene silencing in MM. MIR203 is a tumour suppressor microRNA inhibiting cellular proliferation by targeting CREB1 mRNA in MM. Comparable occurrence of MIR203 methylation in MGUS and MM at diagnosis or relapse suggested that MIR203 methylation may be an early event in myelomagenesis instead of being acquired during disease progression. © 2011 Blackwell Publishing Ltd.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationBritish Journal Of Haematology, 2011, v. 154 n. 5, p. 569-578 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1365-2141.2011.08782.x
 
dc.identifier.citeulike9690490
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1365-2141.2011.08782.x
 
dc.identifier.eissn1365-2141
 
dc.identifier.epage578
 
dc.identifier.hkuros189627
 
dc.identifier.hkuros192229
 
dc.identifier.isiWOS:000294584000004
Funding AgencyGrant Number
Hong Kong Research Grants Council763409M
Funding Information:

This work was supported by the Hong Kong Research Grants Council General Research Fund (Ref. 763409M) awarded to Dr C.S. Chim.

 
dc.identifier.issn0007-1048
2013 Impact Factor: 4.959
 
dc.identifier.issue5
 
dc.identifier.pmid21707582
 
dc.identifier.scopuseid_2-s2.0-80051598906
 
dc.identifier.spage569
 
dc.identifier.urihttp://hdl.handle.net/10722/137366
 
dc.identifier.volume154
 
dc.languageeng
 
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBritish Journal of Haematology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThe definitive version is available at www.blackwell-synergy.com
 
dc.subject.meshBone Marrow - pathology
 
dc.subject.meshEpigenesis, Genetic
 
dc.subject.meshGene Silencing
 
dc.subject.meshMicroRNAs - genetics
 
dc.subject.meshMultiple Myeloma - etiology - genetics
 
dc.subjectHypermethylation
 
dc.subjectMicroRNA
 
dc.subjectMIR203
 
dc.subjectMyeloma
 
dc.subjectTumour suppressor
 
dc.titleEpigenetic silencing of MIR203 in multiple myeloma
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Wong, KY</contributor.author>
<contributor.author>Liang, R</contributor.author>
<contributor.author>So, CC</contributor.author>
<contributor.author>Jin, DY</contributor.author>
<contributor.author>Costello, JF</contributor.author>
<contributor.author>Chim, CS</contributor.author>
<date.accessioned>2011-08-26T14:23:58Z</date.accessioned>
<date.available>2011-08-26T14:23:58Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>British Journal Of Haematology, 2011, v. 154 n. 5, p. 569-578</identifier.citation>
<identifier.issn>0007-1048</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/137366</identifier.uri>
<description.abstract>Epigenetic inactivation of tumour suppressor microRNAs has been implicated in carcinogenesis. We studied the promoter methylation of MIR203 in eight normal marrow controls, eight multiple myeloma (MM) cell lines, 20 monoclonal gammopathy of undetermined significance (MGUS), 123 diagnostic MM and 19 relapsed MM samples by methylation-specific polymerase chain reaction. Promoter of MIR203 was unmethylated in normal controls but homozygously methylated in 25% MM cell lines. Treatment with 5-Aza-2&apos;-deoxycytidine led to promoter demethylation and MIR203 re-expression. Cyclic AMP responsive element binding protein 1 (CREB1) mRNA was predicted as a MIR203 direct target. Luciferase activity was reduced in constructs carrying wild-type CREB1 3&apos;UTR upon MIR203 expression but not in those carrying mutant CREB1 3&apos;UTR. Moreover, restoration of MIR203 led to downregulation of CREB1 protein and inhibition of myeloma cell proliferation. In primary samples, MIR203 methylation occurred in 25.0% MGUS, 23.6% diagnostic MM, and 21.1% relapsed MM samples. In conclusion, MIR203 methylation is disease-specific with reversible gene silencing in MM. MIR203 is a tumour suppressor microRNA inhibiting cellular proliferation by targeting CREB1 mRNA in MM. Comparable occurrence of MIR203 methylation in MGUS and MM at diagnosis or relapse suggested that MIR203 methylation may be an early event in myelomagenesis instead of being acquired during disease progression. &#169; 2011 Blackwell Publishing Ltd.</description.abstract>
<language>eng</language>
<publisher>Blackwell Publishing Ltd. The Journal&apos;s web site is located at http://www.blackwellpublishing.com/journals/BJH</publisher>
<relation.ispartof>British Journal of Haematology</relation.ispartof>
<rights>The definitive version is available at www.blackwell-synergy.com</rights>
<subject>Hypermethylation</subject>
<subject>MicroRNA</subject>
<subject>MIR203</subject>
<subject>Myeloma</subject>
<subject>Tumour suppressor</subject>
<subject.mesh>Bone Marrow - pathology</subject.mesh>
<subject.mesh>Epigenesis, Genetic</subject.mesh>
<subject.mesh>Gene Silencing</subject.mesh>
<subject.mesh>MicroRNAs - genetics</subject.mesh>
<subject.mesh>Multiple Myeloma - etiology - genetics</subject.mesh>
<title>Epigenetic silencing of MIR203 in multiple myeloma</title>
<type>Article</type>
<description.nature>link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1111/j.1365-2141.2011.08782.x</identifier.doi>
<identifier.pmid>21707582</identifier.pmid>
<identifier.scopus>eid_2-s2.0-80051598906</identifier.scopus>
<identifier.hkuros>189627</identifier.hkuros>
<identifier.hkuros>192229</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-80051598906&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>154</identifier.volume>
<identifier.issue>5</identifier.issue>
<identifier.spage>569</identifier.spage>
<identifier.epage>578</identifier.epage>
<identifier.eissn>1365-2141</identifier.eissn>
<identifier.isi>WOS:000294584000004</identifier.isi>
<publisher.place>United Kingdom</publisher.place>
<identifier.citeulike>9690490</identifier.citeulike>
</item>
Author Affiliations
  1. University of California, San Francisco
  2. The University of Hong Kong