C20orf20 (MRG-binding protein) as a potential therapeutic target for colorectal cancer

Abstract

BACKGROUND: Colorectal cancer is one of the most common causes of cancer death worldwide. Using cDNA microarray containing 23 040 genes, we earlier investigated gene-expression profiles in 11 colorectal cancers for the purpose of better understanding of colorectal carcinogenesis as well as development of novel diagnostic and therapeutic strategies. MRG-binding protein (MRGBP) or C20orf20, encoding a subunit of TRRAP/TIP60-containing histone acetyltransferase complex, was up-regulated in the majority of colorectal tumours. METHODS AND RESULTS: The elevated expression of MRGBP was observed in colorectal cancer tissues by quantitative PCR as well as immunohistochemical analyses. MRGBP marginally expressed in normal vital organs. Notably, suppressed MRGBP expression by MRGBP short hairpin RNA inhibited proliferation of colorectal cancer cells. Yeast two-hybrid screening and subsequent immunoprecipitation analysis identified bromodomain containing 8 (BRD8) as an MRGBP-interacting protein. As RNA interference against BRD8 also suppressed proliferation of colorectal cancer cells, BRD8 may be an important down-stream target of MRGBP. CONCLUSION: These results suggest that MRGBP has an important function in proliferation of cancer cells through the regulation of BRD8 and that MRGBP should be a novel therapeutic target for colorectal cancer.

RETRACTED: MiR‐137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP

“…Previous studies suggested that upregulated MRGBP might promote proliferation of colorectal cancer cells through the regulation of BRD8. 7 Furthermore, MRGBP could regulate stability and/or synthesis of both TIP60/HAT complex and HDACs complexes, which are associated with tumor occurrence and advance, as well as aggressive biological behaviors. [24][25][26][27] We previously revealed that MRGBP expression was significantly upregulated in PanCa samples and cell lines.…”

Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma

“…This colorectal cancer study showed that a reduction of C20orf20 expression through stable short-hairpin RNA inhibited proliferation in the colon carcinoma lines HCT116 and SW480 (shown by a 10% decrease in S-phase replicating cells), without evidence of apoptosis (Yamaguchi et al , 2010). We investigated whether C20orf20 knockdown yielded similar results in cSCC and whether any effect on normal keratinocytes was observed.…”

Human Tip60 (NuA4) Complex and Cancer

“…In human colon cancer, MRGBP was upregulated in the majority of the cancers. 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).…”

“…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.…”

“…SiRNA-mediated Brd8 knockdown resulted in cell death in HCT116 and growth delay in DLD1, both are colorectal cancer cells (Yamada and Rao, 2008). With shRNA, an independent lab showed that inhibition of Brd8 resulted in growth inhibition (Yamaguchi et al, 2010), thus Brd8 is suspected to provide survival fitness and growth advantage. In our lab, transcriptome analysis showed little difference in the amount of Brd8 transcripts in colonic normal-looking epithelial and cancer cells, yet the protein accumulates in cancer cells.…”