Ferroptosis-associated ALOX12 suppresses ovarian cancer progression through MAPK signaling pathway

Ovarian cancer (OC) persists as a highly fatal gynecologic tumor, underscoring the urgent need for dependable diagnostic markers and innovative therapeutic strategies. In this study, we identify Arachidonate 12-lipoxygenase (ALOX12) as a previously unrecognized ferroptosis-related tumor suppressive regulator with significant diagnostic and prognostic value in OC. By integrating Weighted Gene Co-expression Network Analysis (WGCNA), machine learning algorithms, and survival modeling, and validating our findings through in vitro and in vivo experiments, transcriptomic profiling, and biochemical assays, we systematically characterized the biological and mechanistic roles of ALOX12. Our analysis revealed that ALOX12 is markedly downregulated in OC tissues, with its low expression correlating with poor clinical outcomes. Functional experiments further demonstrated that ALOX12 suppresses OC cell proliferation, invasion, and migration, while promoting apoptosis and ferroptosis-associated lipid peroxidation. Mechanistically, transcriptome sequencing and protein assays pinpointed MAPK signaling as a key pathway modulated by ALOX12. Additionally, our experiments revealed that ALOX12 exerts its effects by regulating HSPA6 expression. Collectively, these findings highlight ALOX12 as a promising biomarker and potential therapeutic target, offering new insights into ferroptosis-associated signaling networks and their implications for improving the management of OC.