伯基特淋巴瘤中DNMT1、DNMT3B和miR-29s的失调提示其对疾病发病机制有新的作用。
Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis.
作者信息
Robaina Marcela C, Mazzoccoli Luciano, Arruda Viviane Oliveira, Reis Flaviana Ruade de Souza, Apa Alexandre Gustavo, de Rezende Lidia Maria Magalhães, Klumb Claudete Esteves
机构信息
Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Serviço de Hematologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
出版信息
Exp Mol Pathol. 2015 Apr;98(2):200-7. doi: 10.1016/j.yexmp.2015.03.006. Epub 2015 Mar 4.
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.
启动子基因区域的CpG岛甲基化在淋巴瘤中经常可见。DNA甲基化由DNA甲基转移酶（DNMTs）建立。DNMT1维持甲基化模式，而DNMT3A和DNMT3B对DNA从头甲基化至关重要。关于DNMTs在淋巴瘤中的表达知之甚少。DNMT3A和3B基因可在转录后由miR-29家族调控。在此，我们首次证明了DNMT1和DNMT3B在伯基特淋巴瘤（BL）肿瘤样本中过表达（分别为69%和86%）。具体而言，用DNMT抑制剂5-氮杂-2'-脱氧胞苷处理两种BL细胞系可降低DNMT1和DNMT3B蛋白水平并抑制细胞生长。此外，BL肿瘤样本中miR-29a、miR-29b和miR-29c水平显著降低。此外，miR-29a、miR-29b和miR-29c的异位表达降低了DNMT3B的表达，并且miR-29a和miR-29b导致p16(INK4a) mRNA表达增加。总之，我们的数据表明DNMT1、DNMT3B和miR29的失调可能参与BL的发病机制。
Zotero 插件