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Article: Epigenetic silencing of MIR203 in multiple myeloma

TitleEpigenetic silencing of MIR203 in multiple myeloma
Authors
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
Citation
British Journal Of Haematology, 2011, v. 154 n. 5, p. 569-578 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/137366
ISSN
2014 Impact Factor: 4.711
2014 SCImago Journal Rankings: 1.768
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorWong, KYen_HK
dc.contributor.authorLiang, Ren_HK
dc.contributor.authorSo, CCen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorCostello, JFen_HK
dc.contributor.authorChim, CSen_HK
dc.date.accessioned2011-08-26T14:23:58Z-
dc.date.available2011-08-26T14:23:58Z-
dc.date.issued2011en_HK
dc.identifier.citationBritish Journal Of Haematology, 2011, v. 154 n. 5, p. 569-578en_HK
dc.identifier.issn0007-1048en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137366-
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.en_HK
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJHen_HK
dc.relation.ispartofBritish Journal of Haematologyen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectHypermethylationen_HK
dc.subjectMicroRNAen_HK
dc.subjectMIR203en_HK
dc.subjectMyelomaen_HK
dc.subjectTumour suppressoren_HK
dc.subject.meshBone Marrow - pathology-
dc.subject.meshEpigenesis, Genetic-
dc.subject.meshGene Silencing-
dc.subject.meshMicroRNAs - genetics-
dc.subject.meshMultiple Myeloma - etiology - genetics-
dc.titleEpigenetic silencing of MIR203 in multiple myelomaen_HK
dc.typeArticleen_HK
dc.identifier.emailLiang, R:rliang@hku.hken_HK
dc.identifier.emailSo, CC:scc@pathology.hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailChim, CS:jcschim@hku.hken_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.identifier.authoritySo, CC=rp00391en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1365-2141.2011.08782.xen_HK
dc.identifier.pmid21707582-
dc.identifier.scopuseid_2-s2.0-80051598906en_HK
dc.identifier.hkuros189627en_US
dc.identifier.hkuros192229-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051598906&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume154en_HK
dc.identifier.issue5en_HK
dc.identifier.spage569en_HK
dc.identifier.epage578en_HK
dc.identifier.eissn1365-2141-
dc.identifier.isiWOS:000294584000004-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWong, KY=36151671200en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK
dc.identifier.scopusauthoridSo, CC=7102919978en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridCostello, JF=7201995909en_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.citeulike9690490-

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