Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Cai,Jun-Yan; Xu,Tong-Tong; Wang,Ye; Chang,Jing-Jian; Li,Jian; Chen,Xiao-Yang; Chen,Xi; Yin,Yi-Fei; Ni,Xue-Jun

doi:10.3892/ijo.2018.4564

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Authors:
- Jun-Yan Cai
- Tong-Tong Xu
- Ye Wang
- Jing-Jian Chang
- Jian Li
- Xiao-Yang Chen
- Xi Chen
- Yi-Fei Yin
- Xue-Jun Ni
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Affiliations: Department of Rehabilitation, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, School of Medicine, Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Ultrasound, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: September 18, 2018 https://doi.org/10.3892/ijo.2018.4564
Pages: 2758-2768

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Abstract

Glioma is the most lethal type of primary brain tumor characterized by aggressiveness and a poor prognosis. Histone deacetylase 4 (HDAC4) is frequently dysregulated in human malignancies. However, its biological functions in the development of glioma are not fully understood. The present study aimed to evaluate HDAC4 expression in human glioma and to elucidate the mechanistic role of HDAC4 in glioma. The results suggested that HDAC4 was significantly upregulated in glioma tissues and a number of glioma cell lines compared with adjacent non-tumor tissues and the non-cancerous human glial cell line SVG p12, respectively (P<0.05). The proliferation, adenosine triphosphate (ATP) levels and invasion ability were substantially enhanced in U251 cells with HDAC4 overexpression, and suppressed in U251 cells with a knockdown of HDAC4 compared with that in U251 cells transfected with the negative control. Knockdown of HDAC4 resulted in cell cycle arrest at the G0/G1 phase and induced the increase of reactive oxygen species level in U251 cells. Furthermore, HDAC4 overexpression was revealed to substantially inhibit the expression of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and the expression of E-cadherin and β‑catenin in glioma U251 cells. Knockdown of HDAC4 substantially promoted the expression of CDK1 and CDK2 and vimentin in glioma U251 cells. Mechanistically, the results of the present study demonstrated that HDAC4 displayed a significant upregulation in glioma, and promoted glioma cell proliferation and invasion mediated through the repression of p21, p27, E-cadherin and β‑catenin, and the potentiation of CDK1, CDK2 and vimentin. Altogether, the present study revealed that HDAC4 overexpression was central for the tumorigenesis of glioma, which may serve as a useful prognostic biomarker and potential therapeutic target for glioma.

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