학술논문

Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies
Document Type
Academic Journal
Source
PLoS ONE. April 22, 2011, Vol. 6 Issue 4, e19027
Subject
Methylation
Histones
Non-Hodgkin's lymphomas
Multiple myeloma
Cancer
Epigenetic inheritance
Health
Science and technology
Language
English
ISSN
1932-6203
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
Author(s): Kwan Yeung Wong 1 , Chi Chiu So 2 , Florence Loong 2 , Lap Ping Chung 2 , William Wai Lung Lam 3 , Raymond Liang 1 , [...]