title: Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.
abstract: Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia.
authors: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740 - Ed. Leitão da Cunha - 1ºandar, São Paulo, 04023-900, SP, Brazil.
authors: Thaís Brilhante
authors: TB
authors: Pontes
authors: Elizabeth Suchi
authors: ES
authors: Chen
authors: Carolina Oliveira
authors: CO
authors: Gigek
authors: Danielle Queiroz
authors: DQ
authors: Calcagno
authors: Fernanda
authors: F
authors: Wisnieski
authors: Mariana Ferreira
authors: MF
authors: Leal
authors: Samia
authors: S
authors: Demachki
authors: Paulo Pimentel
authors: PP
authors: Assumpção
authors: Ricardo
authors: R
authors: Artigiani
authors: Laércio Gomes
authors: LG
authors: Lourenço
authors: Rommel Rodriguez
authors: RR
authors: Burbano
authors: Marília
authors: M
authors: Arruda Cardoso Smith
mesh_terms: D000328:Adult; D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C489325:MBD2 protein, human; C115369:MBD3 protein, human; D012333:RNA, Messenger