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Published on: February 9, 2024
Knockdown of RAD51AP1 suppressed cell proliferation and invasion in esophageal squamous cell carcinoma
Yang-Yang Hu1, Chen-Chao Ma1, Kai-Xing Ai2
1Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No.507, Zhengmin Road, Shanghai, 200433, China.
Background:
Esophageal cancer is a common malignant tumor of digestive tract with esophageal squamous cell carcinoma (ESCC) being the main histological subtype. This study aimed to identify potential hub gene associated with the pathophysiology of ESCC through bioinformatics analysis and experiment validation.
Methods:
Three microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. The overlapping differentially expressed genes (DEGs) were analyzed by GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway analyses were performed to predict the potential functions of DEGs. Nine hub genes were identified using protein-protein interaction (PPI) network and Cytoscape software. We selected RAD51-associated protein 1 (RAD51AP1) for further research because of its poor prognosis and it has not been sufficiently studied in ESCC. The effects of RAD51AP1 on proliferation, apoptosis, migration and invasion of ESCC cells were determined by in vitro functional assays.
Results:
RAD51AP1 expression was significantly upregulated in ESCC tissues compared with normal tissues by using The Cancer Genome Atlas (TCGA) database. High expression of RAD51AP1 was associated with worse survival in ESCC patients. RAD51AP1 expression was positively associated with the enrichment of Th2 cells and T helper cells. Furthermore, CCK-8 and colony formation assays showed knockdown of RAD51AP1 inhibited the proliferation of ESCC cells. Flow cytometry analysis indicated knockdown of RAD51AP1 induced cell cycle arrest and apoptosis in ESCC cells. Transwell assay revealed knockdown of RAD51AP1 suppressed the migration and invasion of ESCC cells.
Conclusions:
Finally, our results demonstrated that RAD51AP1 silencing significantly inhibited cell proliferation and invasion in ESCC, thereby highlighting its potential as a novel target for ESCC treatment.
Insights
RAD51AP1 is highly expressed in esophageal squamous cell carcinoma (ESCC) and drives cancer progression. Silencing RAD51AP1 inhibits ESCC cell proliferation and invasion, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is a significant global health concern.
- Identifying key molecular drivers is crucial for developing effective ESCC treatments.
Purpose of the Study:
- To identify novel hub genes implicated in ESCC pathophysiology using bioinformatics and experimental validation.
- To investigate the functional role of RAD51-associated protein 1 (RAD51AP1) in ESCC progression.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases for differential gene expression analysis.
- Constructed a protein-protein interaction (PPI) network using Cytoscape to identify hub genes.
- Performed in vitro functional assays (CCK-8, colony formation, flow cytometry, Transwell) to assess the impact of RAD51AP1 knockdown on ESCC cells.
Main Results:
- RAD51AP1 was significantly upregulated in ESCC tissues and associated with poorer patient survival.
- RAD51AP1 knockdown inhibited ESCC cell proliferation, induced cell cycle arrest, and promoted apoptosis.
- Silencing RAD51AP1 suppressed ESCC cell migration and invasion.
Conclusions:
- RAD51AP1 plays a critical role in promoting ESCC cell proliferation and invasion.
- RAD51AP1 represents a promising novel therapeutic target for esophageal squamous cell carcinoma treatment.
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