CENPN contributes to pancreatic carcinoma progression through the MDM2-mediated p53 signaling pathway.

Abstract

Introduction: We undertook an in-depth investigation of the data pertaining to pancreatic adenocarcinoma (PAAD) to identify potential targets for the development of precision therapies.

Material and methods: The construction of a protein-protein interaction (PPI) network was based on overlapping differentially expressed genes (DEGs) identified in the GSE16515, GSE32676, and GSE125158 datasets. A subsequent bioinformatic analysis was performed on the interconnected genes within the PPI network, leading to the identification of the central gene, CENPN. In vitro experimentation such as CCK8 and Transwell experiments was employed to elucidate the impact of CENPN expression patterns on PAAD cell proliferation, migration, and invasion. Furthermore, the investigation revealed through comprehensive enrichment analysis that the pivotal signaling pathway associated with CENPN is the p53 signaling pathway.

Results: Following a comprehensive bioinformatic analysis of 161 concordant differentially expressed genes (DEGs) across three microarray datasets, CENPN emerged as the central gene under investigation. Overexpression of CENPN in pancreatic adenocarcinoma (PAAD) was associated with unfavorable patient outcomes and heightened sensitivity to four PAAD therapies: gemcitabine, docetaxel, paclitaxel, and sunitinib. Reduced CENPN expression impeded PAAD cell proliferation, migration, and invasion; however, these effects were counteracted upon upregulation of CENPN expression. Additionally, CENPN interacted with MDM2, promoting PAAD progression by targeting the p53 signaling pathway.

Conclusions: The findings of our study substantiate that CENPN is associated with the pathogenesis of PAAD. Consequently, CENPN appears to be a promising candidate for targeted precision therapy in clinical applications.