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.
Highlights
Brain glioma is one of the most common malignant brain tumors, accounting for about 40% of the total brain tumors and 80% of all malignant brain tumors [1]
These results suggested that targeting jumonji domain-containing protein 3 (JMJD3) has potential clinical value in the glioma treatment
These results indicated that levels of JMJD3 mRNA and protein were obviously increased in glioma cells U87 and U251 compared to hCMEC (Figure 2A and 2B), while the content of H3K27me3 was reduced (Figure 2B)
Summary
Brain glioma is one of the most common malignant brain tumors, accounting for about 40% of the total brain tumors and 80% of all malignant brain tumors [1]. It is of great significance to explore new therapeutic strategies for glioma. A series of research advances on glioma mechanism provide numerous therapeutic targets [3]. Epigenetic abnormity is an important factor of gliomas development [4]. The studies on paediatric glioblastoma provide new clues for gliomas development [5]. There are 31% mutations in H3F3A gene which codes histone 3 variant H3.3 [6]. The commonest H3F3A mutations lead to amino acid substitutions at lysine (K) 27 to methionine (M) (K27M) [7]. The K27M mutation can reduce H3K27me levels and activate gene expression [8], which is considered as main cause of K27M mutation related tumorigenesis
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