1. Histone deacetylase 1 promotes glioblastoma cell proliferation and invasion via activation of PI3K/AKT and MEK/ERK signaling pathways
- Author
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Guozheng Xu, Xiaohong Yin, Xiangyu Wang, Shun Li, Xiao-ping Tang, Jun Wen, Long Zhao, Kashif Rafiq Zahid, Xiangrong Chen, Jie Duan, Maoying Zhang, Liu Zhang, Jun-wei Duan, Yuanchuan Wang, and Lifang Mao
- Subjects
0301 basic medicine ,Adult ,Male ,animal structures ,Adolescent ,MAP Kinase Signaling System ,Histone Deacetylase 1 ,Transfection ,03 medical and health sciences ,Mice ,Phosphatidylinositol 3-Kinases ,Young Adult ,Glioma ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,U87 ,RNA, Small Interfering ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Aged ,Cell Proliferation ,Gene knockdown ,Mice, Inbred BALB C ,Chemistry ,Brain Neoplasms ,General Neuroscience ,Middle Aged ,medicine.disease ,HDAC1 ,Gene Expression Regulation, Neoplastic ,enzymes and coenzymes (carbohydrates) ,030104 developmental biology ,Ki-67 Antigen ,Cell culture ,embryonic structures ,Cancer research ,Female ,Neurology (clinical) ,biological phenomena, cell phenomena, and immunity ,Signal transduction ,Glioblastoma ,Proto-Oncogene Proteins c-akt ,Developmental Biology ,Signal Transduction - Abstract
Histone deacetylase 1 (HDAC1) plays a crucial role in cancer progression and development. This enzyme has been confirmed to be a key regulator of tumor biology functions, such as tumor cell proliferation, migration and invasion. However, HDAC1 expression in glioma remains controversial, and its specific function and molecular mechanism in glioblastoma is poorly understood. In this study, our findings demonstrated that protein and mRNA levels of HDAC1 were increased in glioma cell lines and glioma tissues compared to normal glial cell lines and non-neoplastic brain tissues, respectively. Furthermore, HDAC1 knockdown cells displayed decreased proliferation and invasion capabilities, whereas HDAC1 overexpressing glioblastoma cells displayed more proliferation and invasion capabilities in vitro. These novel outcomes suggested that knockdown of HDAC1 possibly suppressed the expression of phosphorylated AKT (p-AKT) and phosphorylated ERK (p-ERK) proteins, while overexpression of HDAC1 significantly increased p-AKT and p-ERK protein in glioblastoma cells. In addition, knockdown of HDAC1 repressed subcutaneous tumor growth in vivo, and led to down-regulation of p-AKT and p-ERK protein in U87 MG xenograft tumors. For the first time, we have demonstrated that HDAC1 promotes proliferation and invasion in glioblastoma cells by activating PI3K/AKT and MEK/ERK signaling pathways in vitro and in vivo. These results suggest that HDAC1 may be a novel biomarker and potential therapeutic target in glioblastoma.
- Published
- 2018