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

Autor: Chor Sang Chim, Dong-Yan Jin, Lap Ping Chung, Chi Chiu So, Raymond Liang, George K. H. Li, William Wai Lung Lam, Florence Loong, Kwan Yeung Wong
Rok vydání: 2011
Předmět:
Male
Myeloid
Lymphoma
Chronic lymphocytic leukemia
lcsh:Medicine
Gene Expression
Epigenesis
Genetic
Hematologic Cancers and Related Disorders
Lymphoma - genetics
immune system diseases
hemic and lymphatic diseases
Molecular Cell Biology
T-cell lymphoma
lcsh:Science
Chronic Lymphoblastic Leukemia
Aged
80 and over
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Lymphoma
Non-Hodgkin
Hematologic Neoplasms - genetics
Histone Modification
Hematology
Middle Aged
Acute Lymphoblastic Leukemia
Leukemia
Myeloid
Acute
Leukemia
medicine.anatomical_structure
Oncology
Hematologic Neoplasms
DNA methylation
Azacitidine
Medicine
Epigenetics
Lymphomas
Female
Multiple Myeloma
Research Article
Acute Myeloid Leukemia
Adult
Antimetabolites
Antineoplastic
Chromatin Immunoprecipitation
Blotting
Western
Biology
Methylation
Molecular Genetics
Epigenesis
Genetic - genetics
Young Adult
Cell Line
Tumor
Acute lymphocytic leukemia
Leukemias
Genetics
Cancer Genetics
medicine
Humans
MicroRNAs - genetics
Myelomas and Lymphoproliferative Diseases
Aged
Clinical Genetics
lcsh:R
Cancers and Neoplasms
Cyclin-Dependent Kinase 6
medicine.disease
Leukemia
Lymphocytic
Chronic
B-Cell
MicroRNAs
Immunology
Cancer research
Leukemia
Lymphocytic
Chronic
B-Cell - genetics
lcsh:Q
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 4, p e19027 (2011)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0019027
Popis: 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.
published_or_final_version
Databáze: OpenAIRE
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