Dysregulation of Zinc Finger Protein 395 Contributes to the Pathogenesis of Chondrosarcoma

Introduction: The transcription factor zinc finger protein 395 (ZNF395) is involved in several cellular responses and tumorigenesis. However, the potential role and clinical significance of ZNF395 in chondrosarcoma are not well investigated. This study determines the expression profile, prognostic value and biological function of ZNF395 in human chondrosarcoma. Methods: The mRNA and protein expressions of ZNF395 in fresh chondrosarcomas and the matched adjacent non-tumor tissues were assessed using real-time PCR and immunoblotting, respectively. The protein expression of ZNF395 in chondrosarcoma specimens was evaluated by immunohistochemistry, and the relationships among its protein level, clinicopathological parameters and prognosis were further detected. Cell viability, colony formation, migration, invasion and apoptosis assay were evaluated in chondrosarcoma cells with depletion of ZNF395. Results: The mRNA and protein expressions of ZNF395 in chondrosarcoma tissues were significantly higher than those in the matched adjacent non-tumor tissues and benign cartilage tumors. Clinical analysis displayed that ZNF395 was expressed at higher levels in chondrosarcoma patients with higher histological grade and advanced MSTS stage. Furthermore, we demonstrated that high expression of ZNF395 correlated with a worse overall survival of chondrosarcoma patients. Multivariate Cox regression analysis indicated that ZNF395 was an independent prognostic marker in chondrosarcoma patients. Functional studies revealed that depletion of ZNF395 markedly inhibited cell viability, colony formation, migration and invasion, and promoted apoptosis in chondrosarcoma. Conclusion: These findings suggest that dysregulation of ZNF395 contributes to chondrosarcoma development, and ZNF395 may act as a potent oncogene and serve as a independently prognostic factor, highlight the potential of ZNF395 as a novel biomarker and therapeutic target for chondrosarcoma.