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Article: Epigenetic inactivation of the hsa-miR-203 in haematological malignancies

TitleEpigenetic inactivation of the hsa-miR-203 in haematological malignancies
Authors
KeywordsHypermethylation
Leukaemia
Lymphoma
MicroRNA
Tumour suppressor
Issue Date2011
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838
Citation
Journal Of Cellular And Molecular Medicine, 2011, v. 15 n. 12, p. 2760-2767 How to Cite?
AbstractmiR-203is a tumour suppressor microRNA (miRNA). We studied the methylation ofhsa-miR-203in 150 samples including acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) by methylation-specific PCR, and miRNA expression by stem-loop RT-qPCR.hsa-miR-203promoter was unmethylated in normal controls but homozygously methylated in two AML and four lymphoma cell lines, in which 5-Aza-2′-deoxycytidine treatment led to promoter demethylation andmiR-203re-expression. Restoration ofmiR-203expression in lymphoma cells inhibited cellular proliferation and increased cell death, suggesting an inherent tumour suppressor activity. In primary samples,hsa-miR-203methylation was absent in CML but detected in 5.0% ALL, 10.0% AML, 42.0% CLL and 38.8% of NHL (including six [60.0%] natural killer-cell, nine [40.9%] B-cell and four [23.5%] T cell NHL). Moreover,hsa-miR-203methylation was associated with hypermethylation ofhsa-miR-34a, -124aand-196bin NHL but not CLL. In CLL,hsa-miR-203methylation was associated with a higher presenting Hb level (P= 0.033). The projected 10 year overall survival of the CLL patients was 58.2%, which was impacted by Rai stage and high-risk karyotypes but nothsa-miR-203methylation.hsa-miR-203was more frequently methylated in lymphoid than myeloid malignancies (P= 0.002). In conclusion,miR-203,a tumour suppressor gene, was hypermethylated in a tumour-specific manner with gene silencing.hsa-miR-203was more frequently hypermethylated in lymphoid than myeloid malignancies. In NHL,hsa-miR-203methylation was associated with concomitant methylation of other tumour suppressor miRNAs. The frequenthsa-miR-203methylation in lymphoid malignancies suggested a pathogenetic role ofhsa-miR-203methylation. © 2011 The Authors © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/137370
ISSN
2012 Impact Factor: 4.753
2015 SCImago Journal Rankings: 1.941
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Hong Kong Research Grants Council
Funding Information:

We thank Dr Curtis C. Harris M. D., Chief, Laboratory of Human Carcinogenesis, National Cancer Inst., USA for his expert comments. This work is supported by The University of Hong Kong Seed Funding Programme for Basic Research, and Hong Kong Research Grants Council General Research Fund to Dr. C.S.C.

References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorWong, KYen_HK
dc.contributor.authorLeung, CYen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorHui, PKen_HK
dc.contributor.authorChan, SYen_HK
dc.contributor.authorYu, Len_HK
dc.date.accessioned2011-08-26T14:24:02Z-
dc.date.available2011-08-26T14:24:02Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Cellular And Molecular Medicine, 2011, v. 15 n. 12, p. 2760-2767en_HK
dc.identifier.issn1582-1838en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137370-
dc.description.abstractmiR-203is a tumour suppressor microRNA (miRNA). We studied the methylation ofhsa-miR-203in 150 samples including acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) by methylation-specific PCR, and miRNA expression by stem-loop RT-qPCR.hsa-miR-203promoter was unmethylated in normal controls but homozygously methylated in two AML and four lymphoma cell lines, in which 5-Aza-2′-deoxycytidine treatment led to promoter demethylation andmiR-203re-expression. Restoration ofmiR-203expression in lymphoma cells inhibited cellular proliferation and increased cell death, suggesting an inherent tumour suppressor activity. In primary samples,hsa-miR-203methylation was absent in CML but detected in 5.0% ALL, 10.0% AML, 42.0% CLL and 38.8% of NHL (including six [60.0%] natural killer-cell, nine [40.9%] B-cell and four [23.5%] T cell NHL). Moreover,hsa-miR-203methylation was associated with hypermethylation ofhsa-miR-34a, -124aand-196bin NHL but not CLL. In CLL,hsa-miR-203methylation was associated with a higher presenting Hb level (P= 0.033). The projected 10 year overall survival of the CLL patients was 58.2%, which was impacted by Rai stage and high-risk karyotypes but nothsa-miR-203methylation.hsa-miR-203was more frequently methylated in lymphoid than myeloid malignancies (P= 0.002). In conclusion,miR-203,a tumour suppressor gene, was hypermethylated in a tumour-specific manner with gene silencing.hsa-miR-203was more frequently hypermethylated in lymphoid than myeloid malignancies. In NHL,hsa-miR-203methylation was associated with concomitant methylation of other tumour suppressor miRNAs. The frequenthsa-miR-203methylation in lymphoid malignancies suggested a pathogenetic role ofhsa-miR-203methylation. © 2011 The Authors © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.en_HK
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838en_HK
dc.relation.ispartofJournal of Cellular and Molecular Medicineen_HK
dc.rightsThe definitive version is available at www3.interscience.wiley.com-
dc.subjectHypermethylationen_HK
dc.subjectLeukaemiaen_HK
dc.subjectLymphomaen_HK
dc.subjectMicroRNAen_HK
dc.subjectTumour suppressoren_HK
dc.titleEpigenetic inactivation of the hsa-miR-203 in haematological malignanciesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1582-1838&volume=15&issue=12&spage=2760&epage=2767&date=2011&atitle=Epigenetic+inactivation+of+the+hsa-miR-203+in+haematological+malignancies-
dc.identifier.emailChim, CS: jcschim@hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1582-4934.2011.01274.xen_HK
dc.identifier.pmid21323860-
dc.identifier.scopuseid_2-s2.0-82155184350en_HK
dc.identifier.hkuros189639en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-82155184350&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2760en_HK
dc.identifier.epage2767en_HK
dc.identifier.isiWOS:000297855700021-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridWong, KY=36151671200en_HK
dc.identifier.scopusauthoridLeung, CY=34979911800en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridHui, PK=35869139500en_HK
dc.identifier.scopusauthoridChan, SY=54411927800en_HK
dc.identifier.scopusauthoridYu, L=7404163935en_HK

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