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Article: Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms

TitleMethylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms
Authors
Issue Date2011
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.translational-medicine.com/home/
Citation
Journal of Translational Medicine, 2011, v. 9 n. 1, article no. 197 How to Cite?
AbstractBACKGROUND: MicroRNA (miR) miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis. METHODS: We studied DNA methylation of these miRs in Philadelphia-negative (Ph-ve) myeloproliferative neoplasms (MPNs). Methylation-specific PCR (MSP), verified by direct sequencing of the methylated MSP products, was performed in cell lines, normal controls and diagnostic marrow samples of patients with MPNs. RESULTS: Methylation of these miRs was absent in the normal controls. miR-34b/c were homozygously methylated in HEL cells but heterozygously in MEG-01. In HEL cells, homozygous miR-34b/c methylation was associated with miR silencing, and 5-aza-2'-deoxycytidine treatment led to re-expression of both miR-34b and miR-34c, consistent with that both miRs are under the regulation of the same promoter CpG island. miR-34a was heterozygously methylated in MEG-01 and K-562. miR-203 was completely unmethylated in K-562 and SET-2 but no MSP amplification was found in both HEL and MEG-01, suggestive of miR deletion. In primary samples, four each had miR-34b/c and -203 methylation, in which two had concomitant methylation of miR-34b/c and -203. miR-34a was methylated in one patient and none had methylation of miR-124-1. Seven patients (15.6%) had methylation of at least one of the four miRs. miR methylation did not correlate with clinical parameters, disease complications or JAK2 V617F mutation. CONCLUSION: This is the first report of miR hypermethylation in MPNs. miR-203 hypermethylation is not specific to Ph+ve leukemias but also present in Ph-ve MPNs. miR-34b/c methylation was associated with reversible miR silencing. There was no correlation of miR methylation with clinical demographic data or outcome.
Persistent Identifierhttp://hdl.handle.net/10722/152740
ISSN
2015 Impact Factor: 3.694
2015 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorWan, TSen_HK
dc.contributor.authorWong, KYen_HK
dc.contributor.authorFung, TKen_HK
dc.contributor.authorDrexler, HGen_HK
dc.contributor.authorWong, KFen_HK
dc.date.accessioned2012-07-16T09:47:27Z-
dc.date.available2012-07-16T09:47:27Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal of Translational Medicine, 2011, v. 9 n. 1, article no. 197en_HK
dc.identifier.issn1479-5876en_HK
dc.identifier.urihttp://hdl.handle.net/10722/152740-
dc.description.abstractBACKGROUND: MicroRNA (miR) miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis. METHODS: We studied DNA methylation of these miRs in Philadelphia-negative (Ph-ve) myeloproliferative neoplasms (MPNs). Methylation-specific PCR (MSP), verified by direct sequencing of the methylated MSP products, was performed in cell lines, normal controls and diagnostic marrow samples of patients with MPNs. RESULTS: Methylation of these miRs was absent in the normal controls. miR-34b/c were homozygously methylated in HEL cells but heterozygously in MEG-01. In HEL cells, homozygous miR-34b/c methylation was associated with miR silencing, and 5-aza-2'-deoxycytidine treatment led to re-expression of both miR-34b and miR-34c, consistent with that both miRs are under the regulation of the same promoter CpG island. miR-34a was heterozygously methylated in MEG-01 and K-562. miR-203 was completely unmethylated in K-562 and SET-2 but no MSP amplification was found in both HEL and MEG-01, suggestive of miR deletion. In primary samples, four each had miR-34b/c and -203 methylation, in which two had concomitant methylation of miR-34b/c and -203. miR-34a was methylated in one patient and none had methylation of miR-124-1. Seven patients (15.6%) had methylation of at least one of the four miRs. miR methylation did not correlate with clinical parameters, disease complications or JAK2 V617F mutation. CONCLUSION: This is the first report of miR hypermethylation in MPNs. miR-203 hypermethylation is not specific to Ph+ve leukemias but also present in Ph-ve MPNs. miR-34b/c methylation was associated with reversible miR silencing. There was no correlation of miR methylation with clinical demographic data or outcome.en_HK
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.translational-medicine.com/home/en_HK
dc.relation.ispartofJournal of Translational Medicineen_HK
dc.rightsJournal of Translational Medicine. Copyright © BioMed Central Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshBone Marrow Neoplasms - genetics-
dc.subject.meshDNA Methylation - drug effects - genetics-
dc.subject.meshMicroRNAs - genetics - metabolism-
dc.subject.meshMyeloproliferative Disorders - genetics-
dc.subject.meshPhiladelphia Chromosome-
dc.titleMethylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasmsen_HK
dc.typeArticleen_HK
dc.identifier.emailChim, CS: jcschim@hku.hken_HK
dc.identifier.emailWan, TS: wantsk@hku.hk-
dc.identifier.emailWong, KY: kwanumu@hku.hk-
dc.identifier.emailFung, TK: fungtk@hku.hk-
dc.identifier.authorityChim, CS=rp00408en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1479-5876-9-197en_HK
dc.identifier.pmid22082000-
dc.identifier.pmcidPMC3283527-
dc.identifier.scopuseid_2-s2.0-81055131632en_HK
dc.identifier.hkuros200920en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-81055131632&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume9en_HK
dc.identifier.issue1, article no. 197en_HK
dc.identifier.isiWOS:000300955400001-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWong, KF=37096553800en_HK
dc.identifier.scopusauthoridDrexler, HG=7202338279en_HK
dc.identifier.scopusauthoridFung, TK=54389057000en_HK
dc.identifier.scopusauthoridWong, KY=36151671200en_HK
dc.identifier.scopusauthoridWan, TS=25623981600en_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.citeulike10037148-

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