Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis.
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.
Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Marcela C
MC
Robaina
Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Luciano
L
Mazzoccoli
Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Viviane Oliveira
VO
Arruda
Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Flaviana Ruade de Souza
FR
Reis
Serviço de Hematologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Alexandre Gustavo
AG
Apa
Divisão de Patologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Lidia Maria Magalhães
LM
de Rezende
Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Electronic address: cklumb@inca.gov.br.
Claudete Esteves
CE
Klumb
D000293:Adolescent; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D000097584:DNA Methyltransferase 3B
D001374:Azacitidine; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003570:Cytidine Triphosphate; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D035683:MicroRNAs; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C532045:MIRN29a microRNA, human; C038673:5-aza-2'-deoxycytidine-5'-triphosphate; C000619380:DNMT1 protein, human
Burkitt lymphoma; DNMT1; DNMT3A; DNMT3B; Decitabine; miR-29 family