Oncogenic role of PLOD3 mediated by SOX9 through IL-6/JAK/STAT3 pathway in cervical cancer

As a major global health challenge, cervical cancer remains poorly understood in terms of its underlying molecular mechanisms, a limitation that hinders the development of targeted therapies. This study investigated the role of PLOD3 in cervical cancer progression and its regulatory pathways. Bioinformatic analysis and clinical sample validation revealed that cervical cancer tissues exhibited increased accumulation of PLOD3, related to poor survival prognosis. Functional experiments demonstrated that PLOD3 silencing restrained cell proliferation, clone formation, migration, invasion, and angiogenesis, while inducing apoptosis in cervical cancer. Mechanistically, the transcription factor SOX9 directly bound to the PLOD3 promoter to activate its transcription, as confirmed by dual-luciferase reporter assays, EMSA, and ChIP-qPCR. Rescue experiments showed that PLOD3 overexpression reversed the anti-tumor effects of SOX9 knockdown, indicating a SOX9/PLOD3 regulatory axis. Further studies revealed that PLOD3 promoted cervical cancer progression via inducing the activation of IL-6/JAK/STAT3 signaling pathway, and inhibiting this pathway mitigated PLOD3-mediated oncogenic effects. In vivo experiments using nude mouse models validated that SOX9 knockdown suppressed tumor growth and metastasis through downregulating PLOD3. Collectively, these findings identified PLOD3 as a SOX9-regulated oncogene that drives cervical cancer via the IL-6/JAK/STAT3 pathway, highlighting its possibility as a therapeutic target for cervical cancer.