The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis.
The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis.
复制标题
IRF2/CENP-N/AKT 信号轴通过增加有氧糖酵解促进鼻咽癌细胞的增殖、细胞周期和凋亡抵抗。
DOI：
10.1186/s13046-021-02191-3
复制
发表时间：
2021-12-10
期刊：
影响因子：
--
通讯作者：
Chen SM
中科院分区：
文献类型：
--
作者：
Qi CL;Huang ML;Zou Y;Yang R;Jiang Y;Sheng JF;Kong YG;Tao ZZ;Feng HY;Hua QQ;Bu LH;Chen SM
研究背景着丝粒蛋白N（Centromere protein N，CENP-N）在多种恶性肿瘤中有高表达，但其在鼻咽癌中的作用及机制尚不清楚。在NPC组织和细胞系中证实CENP-N表达水平。建立稳定的CENP-N敲低和过表达NPC细胞系，并在CENP-N敲低后进行转录组测序。进行体外和体内实验以测试NPC细胞中CENP-N敲低的影响。使用ChIP和双荧光素酶报告基因测定来验证IRF 2和CENP-N的组合。Western blot分析、细胞免疫荧光、免疫沉淀和GST pulldown检测证实CENP-N和AKT的联合作用。结果CENP-N在鼻咽癌组织和细胞系中异常高表达，并与癌巢18F-FDG摄取增高和患者预后不良有关。CENP-N敲除后的转录组测序显示，表达改变的基因富集在与葡萄糖代谢、细胞周期调控相关的途径中。CENP-N基因敲低抑制细胞的糖代谢、增殖、细胞周期和促进凋亡。IRF 2是CENP-N的转录因子，并直接促进NPC细胞中CENP-N的表达。CENP-N通过AKT途径影响鼻咽癌细胞的糖代谢、增殖、细胞周期和凋亡。CENP-N在鼻咽癌细胞中与AKT形成复合物。AKT抑制剂（MK-2206）和LDHA抑制剂结论IRF 2/CENP-N/AKT轴通过促进有氧糖酵解、细胞增殖、细胞周期和凋亡抵抗而促进鼻咽癌细胞的恶性生物学行为，IRF 2/CENP-N/AKT信号轴有望成为鼻咽癌治疗的新靶点。
BackgroundCentromere protein N (CENP-N) has been reported to be highly expressed in malignancies, but its role and mechanism in nasopharyngeal carcinoma (NPC) are unknown.MethodsAbnormal CENP-N expression from NPC microarrays of GEO database was analyzed. CENP-N expression level was confirmed in NPC tissues and cell lines. Stable CENP-N knockdown and overexpression NPC cell lines were established, and transcriptome sequencing after CENP-N knockdown was performed. In vitro and in vivo experiments were performed to test the impact of CENP-N knockdown in NPC cells. ChIP and dual luciferase reporter assays were used to verify the combination of IRF2 and CENP-N. Western blot analysis, cellular immunofluorescence, immunoprecipitation and GST pulldown assays were used to verify the combination of CENP-N and AKT.ResultsCENP-N was confirmed to be aberrantly highly expressed in NPC tissues and cell lines and to be associated with high18F-FDG uptake in cancer nests and poor patient prognosis. Transcriptome sequencing after CENP-N knockdown revealed that genes with altered expression were enriched in pathways related to glucose metabolism, cell cycle regulation. CENP-N knockdown inhibited glucose metabolism, cell proliferation, cell cycling and promoted apoptosis. IRF2 is a transcription factor for CENP-N and directly promotes CENP-N expression in NPC cells. CENP-N affects the glucose metabolism, proliferation, cell cycling and apoptosis of NPC cells in vitro and in vivo through the AKT pathway. CENP-N formed a complex with AKT in NPC cells. Both an AKT inhibitor (MK-2206) and a LDHA inhibitor (GSK2837808A) blocked the effect of CENP-N overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and apoptosis resistance.ConclusionsThe IRF2/CENP-N/AKT axis promotes malignant biological behaviors in NPC cells by increasing aerobic glycolysis, and the IRF2/CENP-N/AKT signaling axis is expected to be a new target for NPC therapy.
登录
查看更多内容
影响因子：
5.2
作者：
Liu MT;Chen MK;Huang CC;Huang CY
通讯作者：
Huang CY
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
外泌体 miR-9 通过靶向 MDK 并调节 PDK/AKT 通路抑制鼻咽癌血管生成。
DOI：
10.1186/s13046-018-0814-3
发表时间：
2018-07-13
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Lu J;Liu QH;Wang F;Tan JJ;Deng YQ;Peng XH;Liu X;Zhang B;Xu X;Li XP
通讯作者：
Li XP
Oct4 和 Sox9 对拟青青蟹 Vih 的转录调控
影响因子：
5.2
作者：
Liao J;Zhang Z;Jia X;Zou Z;Liang K;Wang Y
通讯作者：
Wang Y
影响因子：
5.3
作者：
Carneiro, Flavia R. G.;Ramalho-Oliveira, Renata;Viola, Joao P. B.
通讯作者：
Viola, Joao P. B.