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CENPN contributes to pancreatic carcinoma progression through the MDM2-mediated p53 signaling pathway
Ming Xu1, Jie Tang1, Qiong Sun2
1Department of Gastroenterology, Shanghai Pudong New Area People's Hospital, Shanghai, China.
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.
Insights
CENPN is a key gene in pancreatic adenocarcinoma (PAAD) progression, impacting cell behavior and patient outcomes. Targeting CENPN offers a promising strategy for precision therapy in PAAD.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Pancreatic adenocarcinoma (PAAD) remains a significant challenge in oncology, necessitating novel therapeutic targets.
- Understanding the molecular mechanisms driving PAAD progression is crucial for developing effective precision therapies.
Purpose of the Study:
- To identify potential therapeutic targets for pancreatic adenocarcinoma (PAAD) through in-depth data analysis.
- To investigate the role of the central gene CENPN in PAAD pathogenesis and its association with patient outcomes and therapeutic sensitivity.
Main Methods:
- Construction of a protein-protein interaction (PPI) network using differentially expressed genes (DEGs) from multiple PAAD microarray datasets.
- Bioinformatic analysis to identify the central gene (CENPN) and enrichment analysis to determine associated signaling pathways (p53 pathway).
- In vitro experiments (CCK8, Transwell) to assess the functional impact of CENPN expression on PAAD cell proliferation, migration, and invasion.
Main Results:
- CENPN was identified as the central gene from 161 concordant DEGs across three datasets.
- Overexpression of CENPN correlated with poor prognosis and increased sensitivity to gemcitabine, docetaxel, paclitaxel, and sunitinib in PAAD patients.
- Reduced CENPN expression inhibited PAAD cell proliferation, migration, and invasion, with effects reversed upon CENPN upregulation. CENPN interacts with MDM2, influencing the p53 signaling pathway.
Conclusions:
- CENPN plays a significant role in the pathogenesis of pancreatic adenocarcinoma (PAAD).
- CENPN is a potential biomarker for predicting patient outcomes and therapeutic response in PAAD.
- CENPN represents a promising target for developing novel precision therapies for PAAD.
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