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

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• STEAP4 shows altered expression and methylation in prostate cancer (PCa).
• Understanding STEAP4's role is crucial for PCa diagnosis and treatment.

Purpose of the Study:

• To investigate STEAP4's impact on PCa malignancy in vivo and in vitro.
• To elucidate the molecular mechanisms underlying STEAP4's function in PCa.
• To evaluate STEAP4's diagnostic and prognostic value in PCa.

Main Methods:

• Bioinformatic analysis of TCGA-PRAD and GEO datasets (GSE179321, GSE229904, GSE237995).
• In vitro functional assays (viability, invasion, apoptosis, wound healing) with STEAP4 modulation.
• In vivo nude mouse tumor models.
• RNA-sequencing (RNA-seq) to identify differentially expressed genes (DEGs) and hub genes.
• Western blotting to confirm protein expression.

Main Results:

• STEAP4 is overexpressed in PCa tissues and cells, correlating with poorer patient survival.
• STEAP4 knockdown inhibited PCa cell viability, invasion, and migration, while increasing apoptosis.
• RNA-seq identified 234 DEGs upon STEAP4 knockdown, with NOTCH4 as a key regulated hub gene.
• STEAP4 upregulates NOTCH4, promoting PCa proliferation, migration, and invasion.
• STEAP4 overexpression exacerbated tumor burden in vivo, which was reversed by NOTCH4 knockdown.

Conclusions:

• STEAP4 serves as a valuable biomarker for PCa prognosis and diagnosis.
• STEAP4 drives PCa progression by upregulating NOTCH4.
• Targeting the STEAP4-NOTCH4 axis may offer a novel therapeutic strategy for PCa.