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Exp Mol Pathol ; 98(2): 200-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25746661

RESUMO

Methylation of CpG islands in promoter gene regions is frequently observed in lymphomas. DNA methylation is established by DNA methyltransferases (DNMTs). DNMT1 maintains methylation patterns, while DNMT3A and DNMT3B are critical for de novo DNA methylation. Little is known about the expression of DNMTs in lymphomas. DNMT3A and 3B genes can be regulated post-transcriptionally by miR-29 family. Here, we demonstrated for the first time the overexpression of DNMT1 and DNMT3B in Burkitt lymphoma (BL) tumor samples (69% and 86%, respectively). Specifically, the treatment of two BL cell lines with the DNMT inhibitor 5-aza-dC decreased DNMT1 and DNMT3B protein levels and inhibited cell growth. Additionally, miR-29a, miR-29b and miR-29c levels were significantly decreased in the BL tumor samples. Besides, the ectopic expression of miR-29a, miR-29b and miR-29c reduced the DNMT3B expression and miR-29a and miR-29b lead to increase of p16(INK4a) mRNA expression. Altogether, our data suggest that deregulation of DNMT1, DNMT3B and miR29 may be involved in BL pathogenesis.


Assuntos
Linfoma de Burkitt/genética , DNA (Citosina-5-)-Metiltransferases/biossíntese , MicroRNAs/biossíntese , Adolescente , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linfoma de Burkitt/patologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Inibidor p16 de Quinase Dependente de Ciclina/genética , Citidina Trifosfato/análogos & derivados , Citidina Trifosfato/farmacologia , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , DNA Metiltransferase 3B
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