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.

Methyl-CpG-binding domain 3 inhibits epithelial–mesenchymal transition in pancreatic cancer cells via TGF-β/Smad signalling

“…MBD3 expression is described for the first time in pancreatic cancer tissues in different clinicopathological features, at different tumour stages, and is associated with the outcome of patients. Previous studies have determined that MBD3 expression is downregulated in gastric carcinogenesis (Pontes et al , 2014), colon, and lung cancer (Zhu et al , 2004), indicating that reduced MBD3 expression is a potential marker of the carcinogenesis process. In this study, MBD3 expression is lowest in pancreas adenocarcinoma ductal, and reduces progressively with the increase of clinical stage in pancreatic cancer.…”

“…The methods of generating retroviruses encoding reprogramming factors and further infection of NPCs were referenced by previous papers (Pontes et al , 2014). …”

“…Also, removing MBD3 allows deterministic iPSC generation (Brumbaugh and Hochedlinger, 2013). Moreover, several studies have demonstrated that MBD3 is downregulated in gastric carcinogenesis (Pontes et al , 2014), colon, and lung cancer (Zhu et al , 2004). However, the role of MBD3 in pancreatic cancer cells remains to be clarified.…”

Methyl‐CpG‐Binding Protein (MBD) Family: Epigenomic Read‐Outs Functions and Roles in Tumorigenesis and Psychiatric Diseases

“…). The gene located on 18q21 [Hendrich et al, ] has a large CpG island, although the control of MBD2 expression was not associated exclusively to promoter DNA methylation in gastric tissue [Pontes et al, ]. Two isoforms, the longer MDB2a and MBD2c, differ in the C‐terminal region and were recently shown to have a role in the self‐renewing state of stem cells, both enriched at promoter of two master pluripotency regulators, OCT4 and NANOG .…”

“…The exact mechanism of tumorigenesis progression or suppression by MBD2 still remains unclear and appears to be tissue‐specific. Reduced MBD2 expression was reported in gastric cancer when compared to normal gastric mucosa [Pontes et al, ]. In colon cancer, MBD2 has been shown to bind to the aberrantly methylated promoter region of p14 and p16 , tumor suppressor genes, and to cooperate with HDAC to promote gene silencing.…”