Department of Pathology, Harbin Medical University, Harbin, China.
Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, California.
Cancer Res. 2023 Nov 1;83(21):3593-3610. doi: 10.1158/0008-5472.CAN-23-0557.
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.
许多研究提供了有关结直肠癌中发生的基因组和转录组变化的有价值的信息。然而，DNA 改变或 mRNA 表达并不能可靠地预测蛋白质丰度，这部分归因于基因表达的转录后和/或翻译调控。在这项研究中，我们通过评估结直肠癌患者的转录组和蛋白质组特征，以及在结肠上皮细胞和结肠癌细胞中的比较转录组和核糖体保护的 mRNA 分析，确定增加的翻译效率 (TE) 是结直肠癌的一个标志。COPS7B 是在结直肠癌中始终表现出显著 TE 增加和蛋白质升高而没有转录改变的关键基因之一。胰岛素样生长因子 2 mRNA 结合蛋白 3 (IGF2BP3) 增强了 COPS7B mRNA 的 TE，以促进结直肠癌的生长和转移。发现 COPS7B 是核糖体相互作用组的一个组成部分，与核糖体相互作用以促进核糖体生物发生和 mRNA 翻译起始。总之，这项研究揭示了结直肠癌的蛋白质组特征，并强调了升高的 mRNA 翻译是结直肠癌的一个标志。鉴定 IGF2BP3-COPS7B 轴在结直肠癌中升高的蛋白质合成率提供了一个有前途的治疗靶点来治疗这种侵袭性疾病。
IGF2BP3 介导的 COPS7B 表达增加提高了富含 mRNA 翻译和核糖体生物发生途径的基因的翻译效率，促进蛋白质合成并推动结直肠癌的进展。
