STEAP4 facilitates growth, migration, and invasion of prostate carcinoma through upregulation of NOTCH4

Abstract

STEAP4 manifested differential expression and aberrant methylation in prostate cancer (PCa). Therefore, this study proposed to explore the effect of STEAP4 on the PCa malignant phenotype in vivo and in vitro and the possible molecular mechanisms using RNA-seq. The expression of STEAP4 in PCa and its prognostic and diagnostic value was identified using bioinformatics. After exogenous modulation of STEAP4, the effect of STEAP4 on the malignant phenotype of PCa cells was examined using functional assays and nude mouse tumor models. The STEAP4-related differentially expressed genes (DEGs) and the hub genes were characterized using RNA-seq in conjunction with bioinformatics. STEAP4 exhibited high expression in PCa tissues from TCGA-PRAD and GEO datasets (GSE179321, GSE229904, and GSE237995), which predicted lower survival of patients. The STEAP4-associated nomogram model and diagnostic ROC curve had excellent predictive performance (AUC = 0.814). STEAP4 was overexpressed in PCa tissues and cells. Knockdown of STEAP4 effectively decreased the viability, number of invading cells, and wound healing of PCa cells and increased apoptosis. Overexpression of STEAP4 showed the opposite pattern. RNA-seq revealed that knockdown of STEAP4 resulted in 234 DEGs in PCa cells. FGF17, KCNQ2, PDGFRB, and NOTCH4 are hub genes in DEGs. Notably, NOTCH4 was likewise overexpressed in PCa tissues and cells and was regulated by STEAP4. In in vitro experiments, overexpression of NOTCH4 facilitated PCa cell proliferation, migration, and invasion, which was limited by knockdown of STEAP4. In in vivo experiments, overexpression of STEAP4 exacerbated PCa tumor burden, which was rescued by knockdown of NOTCH4. STEAP4 is a valid biomarker for predicting prognosis and diagnosis of PCa patients. STEAP4 contributes to PCa growth, migration, and invasion by upregulating NOTCH4.