title: 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)/tat-interacting 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.
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Michihiro
authors.initials: M
authors.lastname: Sakai
authors.forename: JooHun
authors.initials: J
authors.lastname: Kim
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Tsunesumi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujii
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Ikenoue
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Muto
authors.forename: Rui
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D051548:Histone Acetyltransferases; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C479739:MRGBP protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051548:Histone Acetyltransferases