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Article: Epigenetic inactivation of the miR-124-1 in haematological malignancies

TitleEpigenetic inactivation of the miR-124-1 in haematological malignancies
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 4 How to Cite?
Abstract
miR-124-1 is a tumour suppressor microRNA (miR). Epigenetic deregulation of miRs is implicated in carcinogenesis. Promoter DNA methylation and histone modification of miR-124-1 was studied in 5 normal marrow controls, 4 lymphoma, 8 multiple myeloma (MM) cell lines, 230 diagnostic primary samples of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), MM, and non-Hodgkin's lymphoma (NHL), and 53 MM samples at stable disease or relapse. Promoter of miR-124-1 was unmethylated in normal controls but homozygously methylated in 4 of 4 lymphoma and 4 of 8 myeloma cell lines. Treatment of 5-Aza-2′-deoxycytidine led to miR-124-1 demethylation and re-expression of mature miR-124, which also associated with emergence of euchromatic trimethyl H3K4 and consequent downregulation of CDK6 in myeloma cells harboring homozygous miR-124-1 methylation. In primary samples at diagnosis, miR-124-1 methylation was absent in CML but detected in 2% each of MM at diagnosis and relapse/progression, 5% ALL, 15% AML, 14% CLL and 58.1% of NHL (p&0.001). Amongst lymphoid malignancies, miR-124-1 was preferentially methylated in NHL than MM, CLL or ALL. In primary lymphoma samples, miR-124-1 was preferentially hypermethylated in B- or NK/T-cell lymphomas and associated with reduced miR-124 expression. In conclusion, miR-124-1 was hypermethylated in a tumour-specific manner, with a heterochromatic histone configuration. Hypomethylation led to partial restoration of euchromatic histone code and miR re-expression. Infrequent miR-124-1 methylation detected in diagnostic and relapse MM samples showed an unimportant role in MM pathogenesis, despite frequent methylation found in cell lines. Amongst haematological cancers, miR-124-1 was more frequently hypermethylated in NHL, and hence warrants further study. © 2011 Wong et al.
Persistent Identifierhttp://hdl.handle.net/10722/137369
ISSN
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong200804159005
200811159040
Hong Kong Research Grants Council General Research Fund763409M
Funding Information:

This work was supported by The University of Hong Kong Seed Funding Programme for Basic Research (Code: 200804159005 and 200811159040), and the Hong Kong Research Grants Council General Research Fund (Ref. 763409M) awarded to Dr C.S. Chim. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

Author Affiliations
  1. The University of Hong Kong
  2. Princess Margaret Hospital Hong Kong
DC FieldValueLanguage
dc.contributor.authorWong, KYen_HK
dc.contributor.authorSo, CCen_HK
dc.contributor.authorLoong, Fen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorLam, WWLen_HK
dc.contributor.authorLiang, Ren_HK
dc.contributor.authorLi, GKHen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorChim, CSen_HK
dc.date.accessioned2011-08-26T14:24:00Z-
dc.date.available2011-08-26T14:24:00Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 4en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137369-
dc.description.abstractmiR-124-1 is a tumour suppressor microRNA (miR). Epigenetic deregulation of miRs is implicated in carcinogenesis. Promoter DNA methylation and histone modification of miR-124-1 was studied in 5 normal marrow controls, 4 lymphoma, 8 multiple myeloma (MM) cell lines, 230 diagnostic primary samples of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), MM, and non-Hodgkin's lymphoma (NHL), and 53 MM samples at stable disease or relapse. Promoter of miR-124-1 was unmethylated in normal controls but homozygously methylated in 4 of 4 lymphoma and 4 of 8 myeloma cell lines. Treatment of 5-Aza-2′-deoxycytidine led to miR-124-1 demethylation and re-expression of mature miR-124, which also associated with emergence of euchromatic trimethyl H3K4 and consequent downregulation of CDK6 in myeloma cells harboring homozygous miR-124-1 methylation. In primary samples at diagnosis, miR-124-1 methylation was absent in CML but detected in 2% each of MM at diagnosis and relapse/progression, 5% ALL, 15% AML, 14% CLL and 58.1% of NHL (p&0.001). Amongst lymphoid malignancies, miR-124-1 was preferentially methylated in NHL than MM, CLL or ALL. In primary lymphoma samples, miR-124-1 was preferentially hypermethylated in B- or NK/T-cell lymphomas and associated with reduced miR-124 expression. In conclusion, miR-124-1 was hypermethylated in a tumour-specific manner, with a heterochromatic histone configuration. Hypomethylation led to partial restoration of euchromatic histone code and miR re-expression. Infrequent miR-124-1 methylation detected in diagnostic and relapse MM samples showed an unimportant role in MM pathogenesis, despite frequent methylation found in cell lines. Amongst haematological cancers, miR-124-1 was more frequently hypermethylated in NHL, and hence warrants further study. © 2011 Wong et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshEpigenesis, Genetic - genetics-
dc.subject.meshHematologic Neoplasms - genetics-
dc.subject.meshLeukemia, Lymphocytic, Chronic, B-Cell - genetics-
dc.subject.meshLymphoma - genetics-
dc.subject.meshMicroRNAs - genetics-
dc.titleEpigenetic inactivation of the miR-124-1 in haematological malignanciesen_HK
dc.typeArticleen_HK
dc.identifier.emailSo, CC: scc@pathology.hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.emailLiang, R: rliang@hku.hken_HK
dc.identifier.emailJin, DY: dyjin@hku.hken_HK
dc.identifier.emailChim, CS: jcschim@hku.hken_HK
dc.identifier.authoritySo, CC=rp00391en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0019027en_HK
dc.identifier.pmid21544199-
dc.identifier.pmcidPMC3081325-
dc.identifier.scopuseid_2-s2.0-79955526497en_HK
dc.identifier.hkuros189637en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955526497&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue4en_HK
dc.identifier.spagee19027en_US
dc.identifier.epagee19027en_US
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000290015800033-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWong, KY=36151671200en_HK
dc.identifier.scopusauthoridSo, CC=7102919978en_HK
dc.identifier.scopusauthoridLoong, F=6602794154en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridLam, WWL=7203022037en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK
dc.identifier.scopusauthoridLi, GKH=50262016900en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.citeulike9257474-

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