Article: Epigenetic silencing of MIR203 in multiple myeloma

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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
2011 Impact Factor: 4.941
2011 SCImago Journal Rankings: 0.586
DOIhttp://dx.doi.org/10.1111/j.1365-2141.2011.08782.x
ReferencesReferences in Scopus
DC Field
Value
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.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
2011 Impact Factor: 4.941
2011 SCImago Journal Rankings: 0.586
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
Author Affiliations
  1. University of California, San Francisco
  2. The University of Hong Kong