Abstract
Glioma is the most common malignant tumor of the central nervous system, with a low survival rate of five years worldwide. Although high expression and prognostic value of histone deacetylase 1 (HDAC1) have been recently reported in various types of human tumors, the molecular mechanism underlying the biological function of HDAC1 in glioma is still unclear. We found that HDAC1 was elevated in glioma tissues and cell lines. HDAC1 expression was closely related with pathological grade and overall survival of patients with gliomas. Downregulation of HDAC1 inhibited cell proliferation, prevented invasion of glioma cell lines, and induced cell apoptosis. The expression of apoptosis and metastasis related molecules were detected by RT-PCR and Western blot, respectively, in U251 and T98G cells with HDAC1 knockdown. We found that HDAC1 knockdown upregulated expression of BIM, BAX, cleaved CASPASE3 and E-CADHERIN, and decreased expression of TWIST1, SNAIL and MMP9 in U251 and T98G cells with HDAC1 knockdown. In vivo data showed that knockdown of HDAC1 inhibited tumor growth in nude mice. In summary, HDAC1 may therefore be considered an unfavorable progression indicator for glioma patients, and may also serve as a potential therapeutic target.
Highlights
Malignant glioma, the most common and leading cause of death in cancer regarding the central nervous system in adults, accounting for 45 to 55% of primary intracranial tumors and has been classified according to the 2007 World Health Organization (WHO) classification system as grades II-IV [1]
We detected the mRNA levels of histone deacetylase 1 (HDAC1) using highthroughput RNA-sequencing data from the glioblastoma multiform (GBM) cohort of The Cancer Genome Atlas (TCGA) and observed increased HDAC1 expression in glioma tissues compared with normal brain tissues (Figure 1A)
People demonstrated that the patients with advanced stage, uncontrolled tumor cellular proliferation and poor prognosis showing an increased HDAC1 expression [27, 28], indicating that HDAC1 may as a molecular biomarker play an important role in glioma patients
Summary
The most common and leading cause of death in cancer regarding the central nervous system in adults, accounting for 45 to 55% of primary intracranial tumors and has been classified according to the 2007 World Health Organization (WHO) classification system as grades II-IV [1]. Glioblastoma multiforme (GBM, WHO grade IV) is the most common and biologically aggressive malignant glioma. The overall prognosis of patients with GBM remains poor, with the median survival rate less than 12 months after diagnosis because they are resistant to chemotherapeutic agents [2]. The invasiveness characterization of glioma is produced by uncontrolled cellular proliferation, rapid diffuse infiltration, and high apoptosis resistance of gliomas [3, 4]; little is known about the factors that mediate glioma invasion. Understanding the molecular mechanism involved in glioma tumorigenesis and progression is important for developing novel therapeutic strategies for glioma
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