eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer
eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer
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DOI：
10.1038/onc.2010.422
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发表时间：
2011-01-01
期刊：
影响因子：
8
通讯作者：
Lee, Y-S
中科院分区：
文献类型：
--
作者：
Goh, S-H;Hong, S-H;Lee, Y-S
基因表达的异常调控是肿瘤发生的必要条件。最近的研究表明，癌基因的表达和肿瘤转化是由真核翻译起始因子（eIFs）亚基控制的。在这里，我们专注于eIF3在蛋白质合成及其亚基在癌症中的差异表达中发挥关键作用。最不具特征的非核心亚基eIF3m被证实在人类癌细胞系和结肠癌患者组织中高度表达。通过使用eIF3m特异性小干扰RNA （siRNA）沉默表达，我们证实eIF3m影响人结肠癌细胞系HCT-116的细胞增殖、细胞周期进程和细胞死亡。使用核糖组学方法，我们确定了一个受elif3m影响的基因子集，并表明两个高度代表性的肿瘤发生相关基因MIF和MT2的表达在mRNA水平上受到eIF3m的影响。我们还证实了MT2A下游分子CDC25A的eif3m依赖性调控，这对于HCT-116细胞的细胞周期进展是必要的。这些结果表明，eIF3m介导了人结肠癌中肿瘤发生相关基因的调控。进一步研究肿瘤发生相关基因及其在eif中的调控作用，将为设计靶向治疗癌症提供线索。中华肿瘤杂志（2011）30,398-409；doi: 10.1038 / onc.2010.422;2010年9月13日在线发布
Abnormal regulation of gene expression is essential for tumorigenesis. Recent studies indicate that regulation of oncogene expression and neoplastic transformation are controlled by subunits of eukaryotic translation initiation factors (eIFs). Here we focused on eIF3 performing a pivotal role in protein synthesis and the differential expression of its subunits in cancer. The most uncharacterized non-core subunit eIF3m was confirmed to be highly expressed in human cancer cell lines and colon cancer patient tissues. By expression silencing with eIF3m-specific small interfering RNA (siRNA), we confirmed that eIF3m influences cell proliferation, cell cycle progression and cell death in human colon cancer cell line HCT-116. Using a ribonomics approach, we identified a subset of elF3m-influenced genes and showed that the expression of two highly represented tumorigenesis-related genes, MIF and MT2, were affected by eIF3m at the mRNA level. We also confirmed eIF3m-dependent regulation of MT2A downstream molecule CDC25A, which is necessary for cell cycle progression in HCT-116 cells. These results suggest that eIF3m mediates regulation of tumorigenesis-related genes in human colon cancer. Further investigations on tumorigenesis-related genes and their regulation by eIFs will provide clues for designing targeted therapy for cancer. Oncogene (2011) 30, 398-409; doi: 10.1038/onc.2010.422; published online 13 September 2010