ACOT11 suppresses prostate cancer progression by inhibiting mitochondrial homeostasis and the PI3K/AKT signaling pathway

Abstract Prostate cancer (PCa), a major malignancy in aged males, often advances to castration-resistant prostate cancer (CRPC) within two years with unclear mechanisms. Acyl CoA thioesterase 11 (ACOT11) modulates lipid metabolism and mitochondria, yet its function in PCa remains unclarified. This study investigated ACOT11’s expression, role and mechanism in PCa. RT-qPCR and western blot tested ACOT11 levels in 20 PCa and 20 benign prostatic hyperplasia tissues. siRNA and overexpression plasmids modified ACOT11 in PC3 and DU145 cells; CCK-8, wound healing and Transwell assays assessed cell proliferation, migration and invasion. Flow cytometry, kits and transmission electron microscopy detected mitochondrial function and ultrastructure. Western blot examined PI3K/AKT, mitochondrial and autophagy proteins. ACOT11 was markedly low in PCa samples. ACOT11 silencing boosted PC3 cell malignant phenotypes, while its overexpression suppressed DU145 progression, triggering mitochondrial dysfunction, repressing PI3K/AKT phosphorylation, modulating MFN2/LC3/TSPO and facilitating apoptosis. ACOT11 functions as a PCa tumor suppressor by disrupting mitochondrial homeostasis and blocking PI3K/AKT, serving as a promising CRPC biomarker and therapeutic target.