Histone deacetylase 1 promotes glioblastoma cell proliferation and invasion via activation of PI3K/AKT and MEK/ERK signaling pathways

Autor: 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, Lifang Mao
Rok vydání: 2018
Předmět:
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
Zdroj: Brain research. 1692
ISSN: 1872-6240
Popis: 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.
Databáze: OpenAIRE
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