The RNA-binding protein RBMS3 inhibits the progression of colon cancer by regulating the stability of LIMS1 mRNA.

BACKGROUND: The RNA-binding motif single-stranded interacting protein 3 (RBMS3) is a constituent of the RNA-binding motif (RBM) protein family, which assumes a pivotal role in governing cellular biogenesis processes such as the cell cycle and apoptosis. Despite an abundance of studies elucidating RBMS3's divergent roles in the genesis and advancement of various tumors, its involvement in colon cancer remains enigmatic. METHODS: The present investigation employed data analysis from TCGA and GTEx to unveil that RBMS3 expression demonstrated a diminished presence in colon cancer tissues when juxtaposed with normal colon tissues. The effect of RBMS3 and LIM zinc finger domain 1 (LIMS1) on colon cancer was substantiated via animal models and cellular experiments. The connection between RBMS3 and LIM zinc finger domain 1 (LIMS1) was verified by molecular biology methods. RESULTS: The study conclusively ascertained that augmenting RBMS3 expression quells the proliferation, migration, and invasion of colon cancer cells. Furthermore, the inquiry unveiled a plausible mechanism through which RBMS3 impacts the expression of LIMS1 by modulating its mRNA stability. The investigation ascertained that RBMS3 inhibits the progression of colon cancer by regulating LIMS1. The inhibitory function of LIMS1 and RBMS3 is closely intertwined in colon cancer, with knocking down LIMS1 being able to rescue the inhibitory effect of RBMS3 overexpression on the functionality of colon cancer cell CONCLUSIONS: The discernments delineate RBMS3 as a novel suppressor of cancer via LIMS1, thereby bestowing fresh therapeutic possibilities and illuminating the intricacies of colon cancer.

Role of protein degradation systems in colorectal cancer.

Protein degradation is essential for maintaining protein homeostasis. The ubiquitin‒proteasome system (UPS) and autophagy-lysosome system are the two primary pathways responsible for protein degradation and directly related to cell survival. In malignant tumors, the UPS plays a critical role in managing the excessive protein load caused by cancer cells hyperproliferation. In this review, we provide a comprehensive overview of the dual roles played by the UPS and autolysosome system in colorectal cancer (CRC), elucidating their impact on the initiation and progression of this disease while also highlighting their compensatory relationship. Simultaneously targeting both protein degradation pathways offers new promise for enhancing treatment efficacy against CRC. Additionally, apoptosis is closely linked to ubiquitination and autophagy, and caspases degrade proteins. A thorough comprehension of the interplay between various protein degradation pathways is highly important for clarifying the mechanism underlying the onset and progression of CRC.

The IGF2BP3-COPS7B Axis Facilitates mRNA Translation to Drive Colorectal Cancer Progression.

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. SIGNIFICANCE: 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.

The role of alternative splicing in lung cancer.

Aberrant alternative splicing (AS) events are frequently observed in lung cancer, which can be attributed to aberrant gene AS, alterations in splicing regulatory factors, or changes in splicing regulatory mechanisms. Consequently, the dysregulation of alternative RNA splicing is the fundamental cause of lung cancer. In this review, we have summarized the pivotal role of AS in the development, progression, invasion, metastasis, angiogenesis, and drug resistance of lung cancer. Ultimately, this review emphasizes the potential of AS as biomarkers in lung cancer prognosis and diagnosis, and introduces some applications of AS isoform in the treatment of lung cancer. The comprehension of the AS may provide a glimmer of hope for the eradication of lung cancer.