{"title":"Activation of HDAC8 Can Suppress the Proliferation of Osteosarcoma Cells via <i>TP53</i> and STAT3/ERK Signaling Pathways.","authors":"Liangming Wang, Xiaoming Bai, Xiaolu Zhang, Xinwen Wang, Shiyuan Chen, Shiqiang Wu, Liang Lin","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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 <i>in vivo</i>. Furthermore, the mechanism underlying HDAC8's influence in osteosarcoma was analyzed by western blot assay.</p><p><strong>Results: </strong>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 <i>in vivo</i>.</p><p><strong>Conclusion: </strong>The activation of HDCA8 could contribute negatively to osteosarcoma proliferation, and HDAC8 may represent a valuable therapeutic target in osteosarcoma therapy.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of clinical and laboratory science","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The Annals of Clinical & Laboratory Science
welcomes manuscripts that report research in clinical
science, including pathology, clinical chemistry,
biotechnology, molecular biology, cytogenetics,
microbiology, immunology, hematology, transfusion
medicine, organ and tissue transplantation, therapeutics, toxicology, and clinical informatics.