Investigation of the Effects of Galectin-1 on Enzalutamide Sensitivity and Cellular Functions in Prostate Cancer Cells and Its Clinical Diagnostic Value

Prostate cancer (PCa) is the most common malignancy in men worldwide, with an increasing incidence rate, and many patients are diagnosed at an advanced stage with metastasis, where bone metastasis is the most frequent. Enzalutamide (ENZ) is the first-line treatment for castration-resistant prostate cancer (CRPC) and has shown efficacy in prolonging survival; however, some patients develop drug resistance. Additionally, benign prostatic hyperplasia (BPH) is a common prostate condition in aging men, with symptoms similar to PCa, highlighting the need for improved diagnostic and therapeutic approaches. In the present study, we integrated public databases, RNA sequencing (RNA-Seq), and bioinformatics tools, utilizing CRISPR-Cas9 technology to knock out galectin-1 (LGALS1) in PCa cells to comprehensively investigate its impact on ENZ sensitivity, cellular functions, and the underlying mechanisms. Clinical tissue samples were also analyzed to assess the clinical significance of LGALS family members. Our findings indicated that ENZ sensitivity depends on AR expression, and LGALS1 knockout in AR-expressing cells enhances ENZ sensitivity. RNA-Seq revealed that LGALS1 knockout suppresses energy metabolism and disrupts oxidative stress balance. Additionally, LGALS1 knockout in high-expression cells reduced proliferation, altered the cell cycle, and decreased migration and adhesion. Clinically, both AR and LGALS1 were overexpressed in bone-metastatic PCa, suggesting their potential as therapeutic targets and biomarkers.