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Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies

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...

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Autores principales: Wong, Kwan Yeung, So, Chi Chiu, Loong, Florence, Chung, Lap Ping, Lam, William Wai Lung, Liang, Raymond, Li, George Kam Hop, Jin, Dong-Yan, Chim, Chor Sang
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081325/
https://www.ncbi.nlm.nih.gov/pubmed/21544199
http://dx.doi.org/10.1371/journal.pone.0019027
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author Wong, Kwan Yeung
So, Chi Chiu
Loong, Florence
Chung, Lap Ping
Lam, William Wai Lung
Liang, Raymond
Li, George Kam Hop
Jin, Dong-Yan
Chim, Chor Sang
author_facet Wong, Kwan Yeung
So, Chi Chiu
Loong, Florence
Chung, Lap Ping
Lam, William Wai Lung
Liang, Raymond
Li, George Kam Hop
Jin, Dong-Yan
Chim, Chor Sang
author_sort Wong, Kwan Yeung
collection PubMed
description 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.
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spelling pubmed-30813252011-05-04 Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies Wong, Kwan Yeung So, Chi Chiu Loong, Florence Chung, Lap Ping Lam, William Wai Lung Liang, Raymond Li, George Kam Hop Jin, Dong-Yan Chim, Chor Sang PLoS One Research Article 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. Public Library of Science 2011-04-22 /pmc/articles/PMC3081325/ /pubmed/21544199 http://dx.doi.org/10.1371/journal.pone.0019027 Text en Wong et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wong, Kwan Yeung
So, Chi Chiu
Loong, Florence
Chung, Lap Ping
Lam, William Wai Lung
Liang, Raymond
Li, George Kam Hop
Jin, Dong-Yan
Chim, Chor Sang
Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies
title Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies
title_full Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies
title_fullStr Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies
title_full_unstemmed Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies
title_short Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies
title_sort epigenetic inactivation of the mir-124-1 in haematological malignancies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081325/
https://www.ncbi.nlm.nih.gov/pubmed/21544199
http://dx.doi.org/10.1371/journal.pone.0019027
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