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


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.


CONCLUSIONS
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.
Yamaguchi
K
K
Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Sakai
M
M
Shimokawa
T
T
Yamada
Y
Y
Nakamura
Y
Y
Furukawa
Y
Y
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
D002352:Carrier Proteins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; C099139:BRD8 protein, human; D000092468:Bromodomain Containing Proteins; C479739:MRGBP protein, human