The IGF2BP3-COPS7B axis facilitates mRNA translation to drive colorectal cancer progression.

Abstract

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.