IGF2BP3-COPS7B轴有助于mRNA翻译,推动结直肠癌的进展。
The IGF2BP3-COPS7B axis facilitates mRNA translation to drive colorectal cancer progression.
发表日期:2023 Aug 10
作者:
Jing Tang, Shuoshuo Wang, Mingjiao Weng, Qingyu Guo, Lili Ren, Yan He, Zihan Cui, Mingqi Cong, Minglu Qin, Jia Yu, Rui Su, Xiaobo Li
来源:
CANCER RESEARCH
摘要:
许多研究已经提供了关于结直肠癌(CRC)发生时基因组和转录组变化的宝贵信息。然而,蛋白质丰度无法通过DNA变化或mRNA表达可靠地预测,部分原因是基因表达的转录后调控和/或转录后调控所致。在本研究中,我们通过评估CRC患者的转录组和蛋白质组特征,以及结肠上皮细胞和结肠癌细胞的比较转录组和核糖体保护mRNA分析,确定了增强的翻译效率(TE)作为CRC的标志。COPS7B是一些关键基因之一,它在CRC中既显著增加了TE,又在转录上没有改变的情况下提高了蛋白质水平。IGF2BP3增强了COPS7B mRNA的TE以促进CRC的生长和转移。COPS7B发现是核糖体相互作用组分,与核糖体相互作用以促进核糖体生物合成和mRNA翻译起始。总之,本研究揭示了CRC的蛋白质组特征,并突出了提高的mRNA翻译作为CRC的标志。IGF2BP3-COPS7B轴的鉴定揭示了CRC中增加的蛋白质合成速率,为治疗这种侵袭性疾病提供了有希望的治疗靶点。
Many studies have provided valuable information about genomic and transcriptomic changes that occur in colorectal cancer (CRC). However, protein abundance cannot be reliably predicted by DNA alteration or mRNA expression, which can be partially attributed to post-transcriptional and/or translational regulation of gene expression. In this study, we identified increased translational efficiency (TE) as a hallmark of CRC by evaluating the transcriptomic and proteomic features of CRC patients, along with comparative transcriptomic and ribosome-protected mRNA analysis in colon epithelial cells and colon cancer cells. COPS7B was among the key genes that consistently showed both significant TE increase and protein elevation without transcriptional alteration in CRC. IGF2BP3 enhanced the TE of COPS7B mRNA to promote CRC 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 CRC and highlighted elevated mRNA translation as a hallmark of CRC. The identification of the IGF2BP3-COPS7B axis underlying the increased protein synthesis rate in CRC provided a promising therapeutic target to treat this aggressive disease.