HDAC2 promotes malignant progression by the RBM47/NONO axis in medulloblastoma.
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BACKGROUND: Medulloblastoma (MB) is one of the most prevalent pediatric brain tumors, constituting approximately 20 % of all childhood brain malignancies. The modification of histone acetylation is recognized for its significance in tumor growth and survival. However, its role in MB has been scarcely investigated. Here, we demonstrate that the Histone deacetylase 2 (HDAC2) modulates oncogene expression and promotes tumorigenesis in MB tumors. METHODS: To elucidate the biological roles of HDAC2 in MB, we employed lentivirus-mediated RNA interference (RNAi) to deplete HDAC2. Subsequently, we employed EdU, flow cytometry (FCM), Transwell assay, and cell line-derived xenograft (CDX) models to evaluate the effects of HDAC2 on proliferation, migration and invasion of MB cells. The underlying mechanism of HDAC2 in MB was further investigated using qRT-PCR, Western blot, CHIP-qPCR, and Luciferase reporter assays. RESULTS: We found that HDAC2 is overexpressed in both MB patient tissues and MB cell lines. The knockdown of HDAC2 significantly inhibited the proliferation, migration, and invasion abilities of MB cells. Mechanistically, HDAC2 promoted RBM47 expression through H3K27 deacetylation. The expression of NONO was increased in MB cells overexpressing RBM47. Critically, HDAC2 knockdown enhanced the sensitivity of MB cells to temozolomide treatment. CONCLUSIONS: Our results suggest that HDAC2 plays an oncogenic role in MB. Targeting the HDAC2/RBM47/NONO axis could be a potential therapeutic strategy for MB patients.