Article: Epigenetic inactivation of the miR-124-1 in haematological malignancies
| Title | Epigenetic inactivation of the miR-124-1 in haematological malignancies |
|---|---|
| Authors | Wong, KY1 So, CC1 Loong, F1 Chung, LP1 Lam, WWL2 Liang, R1 Li, GKH1 Jin, DY1 Chim, CS1 |
| Issue Date | 2011 |
| Publisher | Public 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?] DOI: http://dx.doi.org/10.1371/journal.pone.0019027 |
| 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. |
| ISSN | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 |
| DOI | http://dx.doi.org/10.1371/journal.pone.0019027 |
| PubMed Central ID | PMC3081325 |
| References | References in Scopus |
| Grants | Study of tumor suppressor function of miR-124a in non-Hodgkin's lymphoma The role of aberrant promoter methylation of tumor suppressor micro-RNA in chronic lymphocytic leukemia (CLL) |
| dc.contributor.author | Wong, KY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | So, CC | ||||||
| dc.contributor.author | Loong, F | ||||||
| dc.contributor.author | Chung, LP | ||||||
| dc.contributor.author | Lam, WWL | ||||||
| dc.contributor.author | Liang, R | ||||||
| dc.contributor.author | Li, GKH | ||||||
| dc.contributor.author | Jin, DY | ||||||
| dc.contributor.author | Chim, CS | ||||||
| dc.date.accessioned | 2011-08-26T14:24:00Z | ||||||
| dc.date.available | 2011-08-26T14:24:00Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.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. | ||||||
| dc.description.grant | Study of tumor suppressor function of miR-124a in non-Hodgkin's lymphoma | ||||||
| dc.description.grant | The role of aberrant promoter methylation of tumor suppressor micro-RNA in chronic lymphocytic leukemia (CLL) | ||||||
| dc.description.grantcode | 99861 | ||||||
| dc.description.grantcode | 98237 | ||||||
| dc.description.nature | published_or_final_version | ||||||
| dc.identifier.citation | Plos One, 2011, v. 6 n. 4 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0019027 | ||||||
| dc.identifier.citeulike | 9257474 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0019027 | ||||||
| dc.identifier.epage | e19027 | ||||||
| dc.identifier.hkuros | 189637 | ||||||
| dc.identifier.isi | WOS:000290015800033
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. | ||||||
| dc.identifier.issn | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| dc.identifier.issue | 4 | ||||||
| dc.identifier.pmcid | PMC3081325 | ||||||
| dc.identifier.pmid | 21544199 | ||||||
| dc.identifier.scopus | eid_2-s2.0-79955526497 | ||||||
| dc.identifier.spage | e19027 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/137369 | ||||||
| dc.identifier.volume | 6 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | PLoS ONE | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.subject.mesh | Epigenesis, Genetic - genetics | ||||||
| dc.subject.mesh | Hematologic Neoplasms - genetics | ||||||
| dc.subject.mesh | Leukemia, Lymphocytic, Chronic, B-Cell - genetics | ||||||
| dc.subject.mesh | Lymphoma - genetics | ||||||
| dc.subject.mesh | MicroRNAs - genetics | ||||||
| dc.title | Epigenetic inactivation of the miR-124-1 in haematological malignancies | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Princess Margaret Hospital Hong Kong