The Role Of Histone Acetyltransferase GCN5 In Glioma Development

Glioma is the most common primary brain tumors.The prognosis is gene-rally poor.There are many molecular genetic variation mechanism of glioma,B-esides some oncogenes and tumor suppressor genes, there is also have some epigenetics mechanism change.In epigenetics,there are two kinds of the most common adjustment way:histone modification and DNA methylation. Histone acetylation is the most common in the histone modification.Abnormal Histone acetyltransferase (Histone Acetyltransferases and HATs) and Histone acetylati-on enzyme (Histone deacetylases, HDACs) is the most important enzymes in t-he Histone acetylation process.GCN5 is the first histone acetyltransferase identified from yeast. Acetylated Lysine can weaken interaction between histone and DNA, and then increase gene transcription. The lysine acetyltransferase GCN5 regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in glioma development remains elusive.In this study, we reported that GCN5 was frequently overexpressed in human glioma tissues and glioma cell lines both at protein and mRNA level by Western blot and RT-PCR. At the same time,we also prove that GCN5 expression was positive correlated with PCNA and MMP9 in glioma tissues. And GCN5 expression level in high grade glioma was much higher than in low grade glioma tissues. In our serum starvation and releasing model experiment, GCN5 became gradually increased consistent with PCNA level over time. All these results indicated GCN5 was involved in cell development. In U87 and U251 cell lines, by knocking down GCN5 expression with siRNA interfering, we revealed that GCN5 downregulation could effectively suppress cell growth rate, colony formation and cell invasive ability. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, p-ERK1/2, PCNA,MMP9 and increased the expression of p21. In conclusion, GCN5 exhibits critical roles in glioma tumorigenesis by regulating cell proliferation and invasion, suggesting that GCN5 is a potential molecular target for glioma treatment.