MRG‐binding protein contributes to colorectal cancer development

Abstract

MRGBP (MORF4-related gene-binding protein; also known as chromosome 20 open reading frame 20) encodes a subunit of the transformation/transcription domain-associated protein (TRRAP)/tatinteracting protein 60 (TIP60)-containing histone acetyltransferase complex. We previously showed that MRGBP was upregulated in the majority of colorectal tumors, and the enhanced expression was associated with cell proliferation. In this study, we investigated its role in colorectal carcinogenesis and searched for genes regulated by MRGBP. Immunohistochemical staining of 22 adenomas and 47 carcinomas in the colon and rectum showed that high levels of MRGBP expression were observed more frequently in carcinomas (45%) than adenomas (5%), linking its role to malignant properties of colorectal tumors. No clinicopathological factors were associated with the levels MRGBP expression in colorectal cancer. Copy number analysis revealed that gene amplification is involved in the elevated expression. A genome-wide expression analysis identified a total of 41 genes upregulated by MRGBP. These genes were implicated in biological processes, including DNA replication, minichromosome maintenance, and cell division. Theses results suggest that MRGBP contributes to colorectal carcinogenesis through rendering advantages in cell proliferation and/ or division of cancer cells. Our findings might be helpful for the identification of a specific biomarker for colorectal cancer and the development of diagnostic and/or therapeutic approaches. (Cancer Sci

MRGBP as a potential biomarker for the malignancy of pancreatic ductal adenocarcinoma

“…So far, little has been known about the expression pattern and cellular functions of MRGBP in pancreatic cancer. Previous reports have shown that expression of MRGBP was upregulated in colorectal carcinoma and might be associated with the transformation from adenoma to carcinoma in colorectal carcinogenesis [ 9 , 14 ]. Scholars suggested that MRGBP has an important function in proliferation of cancer cells through the regulation of bromodomain containing 8 (BRD8) [ 9 ].…”

“…Scholars suggested that MRGBP has an important function in proliferation of cancer cells through the regulation of bromodomain containing 8 (BRD8) [ 9 ]. In their study, 41 genes were downregulated by MRGBP siRNA, some of which were responsible for DNA replication, such as CDT1, MCM2, MCM5, and MCM7 [ 14 ]. CDT1 and MCM proteins have been shown to be essential for DNA replication.…”

The aspirin metabolite salicylate inhibits lysine acetyltransferases and MUC1 induced epithelial to mesenchymal transition

“…A close interaction partner of the Tip60 complex was found to promote colorectal cancer development 51 . Furthermore, β-catenin, activated after Adenomatous polyposis coli (APC) mutation which occurs in the majority of colon cancers, interacts with and requires Tip60 for activity 52 .…”

Human Tip60 (NuA4) Complex and Cancer

“…These subunits are overexpressed in colon cancer (Yamada and Rao, 2009;Yamaguchi et al,2010Yamaguchi et al, , 2011Carlson et al, 2003;Lauscher et al, 2007;Graudens et al, 2006;Ki et al, 2007). Brd8 plays a role in survival and/or drug resistance of cultured colon cancer cells.…”

“…Inhibition of MRGBP with shRNA in vitro resulted in an inhibition of cell growth (Yamaguchi et al, 2010). High levels of MRGBP expression were observed more frequently in human colonic carcinomas (45%) than adenomas (5%), linking its role to malignant properties of colorectal tumors (Yamaguchi et al, 2011). 4.17 hEaf6/Eaf6/* Human Eaf6 was isolated as a component of Tip60 (NuA4) complex (Doyon et al, 2004).…”