RNA Metabolism Genes as Prognostic Biomarkers and Therapeutic Targets in Colorectal Cancer Based on the Analysis of Single-Cell and Bulk-RNA Sequencing Data

Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a major cause of cancer-related mortality. Increasing evidence suggests that aberrant RNA metabolism contributes to tumour initiation, progression and therapeutic resistance. In this study, we integrated single-cell RNA sequencing and bulk transcriptomic data to identify RNA metabolism-related genes (RMRGs) associated with CRC progression and evaluate their clinical significance. Through comprehensive bioinformatics analyses, 39 differentially expressed RMRGs were identified, with high RMRG activity predominantly enriched in epithelial cell populations. Cell-cell communication analysis revealed enhanced interactions between epithelial cells and other cell types within the tumour microenvironment. Further integration of single-cell and bulk RNA-sequencing datasets identified PCBP3 and NGRN as key prognostic genes. A two-gene prognostic model based on PCBP3 and NGRN was established and validated in independent cohorts, demonstrating favourable predictive performance. Human Protein Atlas data further confirmed the expression of both proteins in colorectal cancer tissues. Immune infiltration analyses indicated that PCBP3 and NGRN were associated with distinct immune-cell infiltration patterns and immunotherapy-related immune status. Functional experiments demonstrated that silencing PCBP3 or NGRN significantly inhibited the proliferation and invasion of HCT116 colorectal cancer cells. Moreover, Western blot analysis suggested that these effects may be mediated, at least in part, through regulation of the PI3K/AKT signalling pathway. Collectively, our findings identify PCBP3 and NGRN as promising prognostic biomarkers and potential therapeutic targets in colorectal cancer and provide new insights into the role of RNA metabolism in colorectal cancer progression and tumour immune regulation.