Objective: Osteosarcoma is the most common malignant bone cancer and is typically associated with poor prognosis. Histone deacetylase 8 (HDAC8) presents as an effective target in anti-tumor treatment in various tumors. As the functions of HDAC8 in osteosarcoma have not been studied thoroughly, our study aims to explore the effects of HDAC8 in osteosarcoma proliferation.
Methods: HDAC8 expression was analyzed in The Cancer Genome Atlas (TCGA)-pan-cancer dataset. The expression of HDAC8 in osteosarcoma cell lines was detected by western blot. TM-2-51, an activator of HDAC8, was taken to promote HDAC8 expression in osteosarcoma cells. Cell Counting Kit-8 (CCK-8) assay was applied to analyze cell viability changes and colony formation while 5-ethynyl-29-deoxyuridine (EdU) assays were used to evaluate cell proliferation. The migration and invasion abilities were analyzed by transwell assay, the distributions of cell cycle were analyzed by flow cytometry, and xenograft models were used to study the effect of HDAC8 activation in vivo. Furthermore, the mechanism underlying HDAC8's influence in osteosarcoma was analyzed by western blot assay.
Results: Our study demonstrated that activation of HDAC8 in osteosarcoma cells can suppress cell viability, proliferation, migration, invasion, and arrest cell cycle of the osteosarcoma cells via TP53 and STAT3/ERK signaling pathway. Xenograft models confirmed that HDAC8 activation can reduce tumor growth in vivo.
Conclusion: The activation of HDCA8 could contribute negatively to osteosarcoma proliferation, and HDAC8 may represent a valuable therapeutic target in osteosarcoma therapy.
Keywords: HDAC8; activation; osteosarcoma; pathways; proliferation.
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