The pharmacological role of histone demethylase JMJD3 inhibitor GSK-J4 on glioma cells

// Aixia Sui 1, 2 , Yongbing Xu 2 , Yitong Li 2 , Qilu Hu 2 , Zeyang Wang 2 , Hongtao Zhang 2 , Junjie Yang 2 , Xiaoqiang Guo 4, 5 and Wenqing Zhao 1, 3 1 Faculty of Graduate Studies, Hebei Medical University, Shijiazhuang 050081, Hebei, China 2 Department of Oncology, Hebei General Hospital, Shijiazhuang 050051, Hebei, China 3 Department of Neurosurgery, Hebei General Hospital, Shijiazhuang 050051, Hebei, China 4 State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China 5 Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, Guangdong, China Correspondence to: Wenqing Zhao, email: hbghwenqingzhao@126.com Xiaoqiang Guo, email: xiaoqiangguo123@163.com Keywords: glioma, histone demethylase, JMJD3, inhibitor, GSK-J4 Abbreviations: JMJD3: jumonji domain-containing protein 3; KDM6B: lysine-specific demethylase 6B; CCK-8: Cell Counting Kit-8; K27M: lysine (K) 27 to methionine (M) mutation Received: March 31, 2017      Accepted: June 28, 2017      Published: August 02, 2017 ABSTRACT Glioma is regarded as the most prevalent malignant carcinoma of the central nervous system, and lack of effective treatment. Thus, the development of new therapeutic strategies targeting glioma is of significant clinical importance. In the present study, histone H3K27 demethylase jumonji domain-containing protein 3 (JMJD3) was investigated as target for glioma treatment. The mRNA of JMJD3 was overexpressed in glioblastoma tissues compared to normal brain tissues ( P <0.05). The content of JMJD3 was also higher in glioma cells than in human brain microvascular endothelial cell (hCMEC), and the corresponding level of H3K27me3 was decreased ( P <0.05). The treatment with JMJD3 specific inhibitor GSK-J4 can increase the content of H3K27me3 in glioma cells, which means the activity of JMJD3 was inhibited. GSK-J4 can inhibit glioma cell proliferation in a concentration dependent and time-dependent manner ( P <0.05). GSK-J4 also induced glioma cell apoptosis and inhibited cell migration ( P <0.05). But there was no obvious effect of GSK-J4 on hCMEC cells. All together, these data suggest that GSK-J4 has important potential in the gliomas treatment.