Abstract P116: Epigenetic Regulation of Sox21 in Brain Tumor

Abstract Epigenetic dysregulation plays a pivotal role in the pathogenesis of brain tumors, contributing to aberrant gene expression and malignant progression. The transcription factor Sox21, a member of the SRY-related HMG-box (SOX) family, has been implicated in neural differentiation and stem cell regulation; however, its role in brain tumors remains largely unexplored. In this study, we investigated the methylation status and expression levels of Sox21 in U87 cells, a human glioblastoma cell line. Methylation-specific PCR (MSP) and bisulfite sequencing revealed that the Sox21 promoter is hypermethylated, correlating with a marked reduction in Sox21 mRNA and protein expression, as determined by RT-PCR and Western blot analysis. To assess the functional consequences of Sox21 restoration, U87 cells were transfected with a Sox21-expressing vector, leading to a robust increase in Sox21 expression. Forced Sox21 expression significantly increased cell proliferation, as measured by MTT assays and flow cytometry, accompanied by a reduction in the proportion of cells in the sub-G1 phase, suggesting a growth-promoting role for Sox21 in glioblastoma cells. These findings indicate that Sox21 downregulation in glioblastoma is mediated, at least in part, by promoter hypermethylation. However, restoring its expression facilitates tumor cell growth. Collectively, our results reveal that Sox21 functions as an oncogene that is epigenetically silenced through DNA hypermethylation in glioblastoma. Citation Format: Tun-Wu Wang, Yu-Wei Leu, Shu-Huei Hsiao. Epigenetic Regulation of Sox21 in Brain Tumor [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P116.