Targeting the URG4 Signaling Axis with Valproic Acid: Implications for Chordoma Therapy

Abstract Chordoma is a rare malignant tumor originating from notochordal remains, characterized by its aggressiveness and elevated recurrence rates. The limited efficacy of traditional therapies necessitates the exploration of new epigenetic targets. Valproic acid (VPA), a histone deacetylase inhibitor, had antiproliferative effects by restoring the expression of tumor suppressor genes. Upregulated gene 4 (URG4), an oncogene involved in cell proliferation and tumor growth, has been discovered as a possible therapeutic target. However, its role in chordoma remains unexplored. This study examined the effects of VPA on the chordoma cell line using multiple assays. Cell viability was evaluated via MTT assay, while cell migration was assessed using the wound healing assay. Clonogenic capacity was analyzed by colony formation assay. The effect of VPA on URG4 gene expression was measured by RT-qPCR. Treatment with 750 µM VPA resulted in a time-dependent reduction in cell viability and migration. The number of colonies was markedly decreased compared with the control group. RT-qPCR analysis revealed that URG4 gene expression was downregulated approximately 4-fold in VPA-treated cells. VPA demonstrated antiproliferative and antimigratory effects on chordoma cells. These findings suggest that VPA may represent a promising epigenetic agent for targeted therapy in chordoma.