Liu Kun, Zhang Qing, Lan Haitao, Wang Liping, Mou Pengfei, Shao Wei, Liu Dan, Yang Wensheng, Lin Zhen, Lin Qingyuan, Ji Tianhai
Department of Pathology, Affiliated Chenggong Hospital, Xiamen University, Xiamen 361000, China.
Chinese People's Liberation Army No. 174 Clinical College, Anhui Medical University, Xiamen 361000, China.
Int J Mol Sci. 2015 Sep 10;16(9):21897-910. doi: 10.3390/ijms160921897.
The general control of nucleotide synthesis 5 (GCN5), which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In the present study, we firstly reported that GCN5 was frequently overexpressed in human glioma tissues and GCN5 was positively correlated with proliferation of cell nuclear antigen PCNA and matrix metallopeptidase MMP9. Meanwhile, down-regulation of GCN5 by siRNA interfering inhibited glioma cell proliferation and invasion. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, PCNA and MMP9 and increased the expression of p21 in glioma cells. In conclusion, GCN5 exhibited critical roles in glioma development by regulating cell proliferation and invasion, which suggested that GCN5 might be a potential molecular target for glioma treatment.
核苷酸合成5(GCN5)的一般控制是一种赖氨酸乙酰转移酶,它调节许多细胞过程,如细胞增殖、分化、细胞周期和DNA损伤修复。然而,其在人类胶质瘤发生发展中的生物学作用仍不清楚。在本研究中,我们首次报道GCN5在人类胶质瘤组织中频繁过表达,且GCN5与细胞核增殖抗原PCNA和基质金属蛋白酶MMP9的增殖呈正相关。同时,通过小干扰RNA(siRNA)干扰下调GCN5可抑制胶质瘤细胞的增殖和侵袭。此外,敲低GCN5可降低胶质瘤细胞中p-STAT3、p-AKT、PCNA和MMP9的表达,并增加p21的表达。总之,GCN5通过调节细胞增殖和侵袭在胶质瘤发生发展中发挥关键作用,这表明GCN5可能是胶质瘤治疗的潜在分子靶点。