The Mechanism Of KAT8 Regulate Cell Proliferation And Tumorigenecity In Glioblastoma

Glioma is the most common and deadly malignant central nervous system tumors. Its greatest feature is have strong aggressive function, than more easily invade the surrounding normal brain tissue. However, surgical clinical treatment can not completely remove the tumor tissue after surgery while the remaining tumor cells may be stimulated from tumor formation, further increasing the degree of invasion of glioblastoma in normal brain tissue. Although neurosurgery technology has greatly improved as well as chemotherapy, radiotherapy and combined therapy and the application of biological treatment, but the prognosis of glioblastoma patients with only 12 months to 15 months. For the poor this stage glioblastoma treatment, we will explore a variety of mechanisms glioblastoma cell proliferation and migration, expected to inhibit the proliferation and invasion of glioblastoma cells induce tumor tissue there is only a certain range; so as to surgery to completely remove the tumor and normal brain tissue aversion to provide assistance for further radiotherapy and chemotherapy.KAT8 is a kind of histion acetylation enzyme and belong to the MYST family. The KAT8 structure containing HAT domain also has extra-territorial structure of chromatin regions and MYST highly conserved domains, the domain consists of coenzyme CoA binding site and C2 HC zinc finger domains. KAT8 originally named Mof, it was identified as part of the Drosophila dosage compensation in. KAT8 addition to histone acetylation sites H4K16 so that overexpression o f the gene, but also make the site of P53 K120 acetylation. This year a variety of experimental results show KAT8 in embryonic formation and development play an important role.In this paper, a preliminary study of the role of KAT8 in glioblastoma tumor ce ll proliferation and investigate possible mechanisms. The results show that in glioblastoma cell lines U87 KAT8 more significant expression of genes, A172, LN229 in both. Use slow disease mediated shRNA interference in gene expression system KAT8 him down, and by qRT-PCR and Western blot to detect the situation down. Use the knockout U87, A172 and LN229 cells in MTT, BrdU labeling technique to detect cell proliferation, showed that cell proliferation was inhibited, the invasion was significantly reduced, while the use of flow cytometry in cell cycle arrest G2 phase, accompanied by down-regulation of protein expression of the corresponding period. Through the establishment of tumor-bearing mice detect KAT8 proliferation and tumor affect the ability of the ind ividual levels of glioblastoma cells. While tumors in mice H & E, IHC, Western and other testing, found a significant decrease in the interference of cells to form tumors, while KAT8 and K i67 expression of the corresponding genes also received two suppression. It found that EGFR signaling pathway is inhibited in the experimental shRNA interference in the system, in Western detected EGFR / AKT / ERK signaling pathway was relevant.In addition, detected the KAT8 expression in glioblastoma cells, proliferation and detected a glioblastoma tumor cells have the ability to significantly improved. Meanwhile EGFR / AKT / ERK signaling pathway in three phosphorylation levels have significantly improved. To confirm KAT8 is to regulate the proliferation of glioblastoma by regulating EGFR / AKT / ERK signaling pathway, tumor formation and invasion. When using cell culture EGFR inhibitors Erlotinid, and by detecting the expression of related genes found in Western KAT8 gene by EGRF / AKT / ERK pathway regulate glioblastoma cell proliferation and invasion. Thereby initially identified by activation of regulating KAT8 mediated EGFR signaling pathway to on glioblastoma cell regulation.