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.
Br J Cancer. 2010 Jan 19;102(2):325-31. doi: 10.1038/sj.bjc.6605500. Epub 2010 Jan 5.
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.
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.
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.
结直肠癌是全球癌症死亡的最常见原因之一。我们使用包含 23040 个基因的 cDNA 微阵列，对 11 例结直肠癌的基因表达谱进行了研究，目的是更好地了解结直肠癌的发生机制，并开发新的诊断和治疗策略。MRG 结合蛋白（MRGBP）或 C20orf20，编码 TRRAP/TIP60 含组蛋白乙酰转移酶复合物的亚基，在大多数结直肠肿瘤中上调。
通过定量 PCR 和免疫组织化学分析观察到结直肠癌细胞中 MRGBP 的表达升高。MRGBP 在正常生命器官中表达微弱。值得注意的是，MRGBP 短发夹 RNA 抑制 MRGBP 的表达抑制了结直肠癌细胞的增殖。酵母双杂交筛选和随后的免疫沉淀分析鉴定出溴结构域包含 8（BRD8）是 MRGBP 的相互作用蛋白。由于针对 BRD8 的 RNA 干扰也抑制了结直肠癌细胞的增殖，BRD8 可能是 MRGBP 的一个重要下游靶标。
这些结果表明，MRGBP 通过调节 BRD8 在癌细胞增殖中具有重要功能，MRGBP 应该是结直肠癌的一个新的治疗靶点。
