Abstract：
Many studies have provided valuable information about genomic and transcriptomic changes that occur in colorectal cancer. However, protein abundance cannot be reliably predicted by DNA alteration or mRNA expression, which can be partially attributed to posttranscriptional and/or translational regulation of gene expression. In this study, we identified increased translational efficiency (TE) as a hallmark of colorectal cancer by evaluating the transcriptomic and proteomic features of patients with colorectal cancer, along with comparative transcriptomic and ribosome-protected mRNA analysis in colon epithelial cells and colon cancer cells. COP9 signalosome subunit 7B (COPS7B) was among the key genes that consistently showed both significant TE increase and protein elevation without transcriptional alteration in colorectal cancer. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) enhanced the TE of COPS7B mRNA to promote colorectal cancer growth and metastasis. COPS7B was found to be a component of the ribo-interactome that interacted with ribosomes to facilitate ribosome biogenesis and mRNA translation initiation. Collectively, this study revealed the proteomic features of colorectal cancer and highlighted elevated mRNA translation as a hallmark of colorectal cancer. The identification of the IGF2BP3-COPS7B axis underlying the increased protein synthesis rate in colorectal cancer provided a promising therapeutic target to treat this aggressive disease.
Increased expression of COPS7B mediated by IGF2BP3 elevates the translational efficiency of genes enriched in mRNA translation and ribosome biogenesis pathways, promoting protein synthesis and driving progression in colorectal cancer.
Increased expression of COPS7B mediated by IGF2BP3 elevates the translational efficiency of genes enriched in mRNA translation and ribosome biogenesis pathways, promoting protein synthesis and driving progression in colorectal cancer.
摘要：
许多研究提供了有关结直肠癌（CRC）中发生的基因组和转录组变化的有价值的信息。然而,蛋白质丰度不能通过DNA改变或mRNA表达可靠地预测，这可以部分归因于基因表达的转录后和/或翻译后调节。在这项研究中,我们通过评估CRC患者的转录组和蛋白质组特征，确定了增加的翻译效率（TE）作为CRC的标志，以及结肠上皮细胞和结肠癌细胞中转录组学和核糖体保护mRNA的比较分析。COPS7B是在CRC中始终显示出显著TE增加和蛋白质升高而没有转录改变的关键基因之一。IGF2BP3增强COPS7BmRNA的TE促进CRC生长和转移。发现COPS7B是与核糖体相互作用以促进核糖体生物发生和mRNA翻译起始的核糖体相互作用的组成部分。总的来说，这项研究揭示了CRC的蛋白质组学特征，并强调了mRNA翻译升高是CRC的标志。作为CRC中蛋白质合成速率增加的基础的IGF2BP3-COPS7B轴的鉴定提供了治疗这种侵袭性疾病的有希望的治疗靶标。
