ANKRD13D drives colorectal cancer progression via p-ERK stabilization-induced MAPK activation

Background The role of ubiquitination modification in colorectal cancer (CRC) has been increasingly recognized. The study was designed to explore key ubiquitination-related genes and their underlying mechanisms in CRC through bioinformatics analysis and experimental validation. Methods Data were obtained from public databases, and ubiquitination-related candidate genes were recognized through differential expression, intersection analyses, univariate Cox regression, and expression trend matching. Subsequently, these genes were ascertained via RT-qPCR in cell lines to identify the key ubiquitination-related gene that has not yet been reported in CRC. The prognostic value and biological functions of the key gene were assessed by survival analysis and enrichment analysis. Finally, a series of in vitro functional assays—such as cell counting kit-8, wound healing, Transwell migration, and co-immunoprecipitation—were performed to explore the molecular mechanisms of the key gene in CRC. Results ANKRD13D was markedly elevated in CRC tissues and cell lines, and its high expression was notably connected with bad prognosis in patients, identifying it as a key ubiquitination-related gene. Enrichment analysis unveiled that ANKRD13D was participated in oxidative phosphorylation and the notch signaling pathway. Functionally, knockdown of ANKRD13D impeded CRC cell proliferation, migration, and invasion. Mechanistically, ANKRD13D was shown to interact with p-ERK protein, enhancing its stability and thereby activating the MAPK signaling pathway. Conclusion ANKRD13D, as a novel prognostic biomarker for CRC, regulates the MAPK signaling pathway by stabilizing p-ERK, suggesting its potential as a therapeutic target.