A Multi-PTM omics atlas uncovers novel aging regulators in colorectal cancer

作者：Yujie Zhang, Wei Zhang, Tianyuan Li, Erjiao Hao, Jie Du, Min Feng, Feng Zhu, Yong Dai · 发表于：BMC Cancer · 年份：2025 · DOI：10.1186/s12885-025-15274-7 · 被引用次数：2 · 研究领域：Protein Tyrosine Phosphatases、Wnt/β-catenin signaling in development and cancer、MicroRNA in disease regulation

BACKGROUND: Aging is a key driver of colorectal cancer (CRC) progression, yet the post-translational modification (PTM) landscape associated with aging in CRC remains largely uncharacterized. In particular, the coordinated influence of multiple PTMs-such as phosphorylation, ubiquitination, and malonylation-on aging-related pathways has not been systematically explored. METHODS: In this study, we established a CRC-specific multiomics framework by profiling phosphorylation, malonylation, and ubiquitination in matched tumor and adjacent normal tissues (n = 8 pairs). The differentially modified proteins were subjected to functional enrichment, protein-protein interaction (PPI) network construction, structural mapping, and aging pathway annotation. Key regulatory axes were reconstructed through integration of GO, KEGG, and literature-based evidence. RESULTS: Aging-related PTMs were extensively dysregulated in CRC, with 162 ubiquitination sites, 64 phosphorylation sites, and 68 malonylation sites altered. LMNB1 has emerged as a multi-PTM protein, indicating coordinated control of the nuclear structure during senescence. PPI network analysis highlighted CDK1, SOD2, and MAPK1 as potential hub PTM-regulated nodes involved in the aging program of CRC. An integrated signaling model further demonstrated how PTM-mediated suppression of the EGFR-RAS axis, along with activation of the p38 and p53 pathways, collectively contributes to shaping the aging phenotype in CRC. CONCLUSION: This stud...