Regulating apoptosis by modulating epidermal growth factor-like domain 7 in renal cell carcinoma

This study aimed to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in renal cell carcinoma (RCC) progression and assess its association with tumor-related biological features through experimental and transcriptomic analyses.

Among RCC cell lines, 786-O cells with high EGFL7 expression were selected for small interfering RNA-mediated knockdown. In vitro assessments, including MTS assay, Annexin V-FITC (fluorescein isothiocyanate)/propidium iodide (PI) flow cytometry, western blotting, and transwell migration/invasion, were employed to evaluate tumor behavior. The in vivo effects were investigated using nude mice xenografts. The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) transcriptome data were analyzed in silico to evaluate clinical relevance.

EGFL7 silencing reduced RCC cell proliferation, migration, and invasion and increased apoptosis in 786-O cells. Annexin V-FITC/PI flow cytometry showed that the apoptotic fraction increased from 5.9% in controls to 10.1% after EGFL7 knockdown (p<0.01), accompanied by increased Bax and cleaved caspase-3 and decreased Bcl-2 expression. Epithelial-mesenchymal transition (EMT) reversal was indicated by increased E-cadherin and decreased N-cadherin and Snail. Xenograft tumors showed reduced volume and weight versus controls (p<0.01). TCGA-KIRC analysis demonstrated higher EGFL7 expression in RCC than normal tissue (p<0.001).

EGFL7 inhibition attenuated RCC cell proliferation, migration, invasion, and EMT while promoting apoptosis in vitro and in vivo. These findings demonstrate an association between EGFL7 expression and key biological processes involved in RCC progression, supporting its potential role as a biomarker of tumor behavior and possible value in enhancing clinical risk stratification and surveillance strategies.