ASPM调控鼻咽癌细胞周期及抑制细胞增殖的作用及机制探讨  

The role and mechanism of ASPM in regulating cell cycle and inhibiting cell proliferation of nasopharyngeal carcinoma

作　　者：杨开炎 覃启才[2] 李旭祥[3] 冯大益[3] 农丰靖 杨秋云 唐凤珠[1] 瞿申红[1] YANG Kaiyan;QIN Qicai;LI Xuxiang;FENG Dayi;NONG Fengjing;YANG Qiuyun;TANG Fengzhu;QU Shenhong(Department of Otorhinolaryngology,Head and Neck,People's Hospital of Guangxi Zhuang Autonomous Region,Guangxi Nanning 530000,China;Department of Otorhinolaryngology,Head and Neck Surgery;Department of Pathology,People's Hospital of Baise,Guangxi Baise 533000,China.)

机构地区：[1]广西壮族自治区人民医院耳鼻咽喉头颈科,广西南宁530000 [2]百色市人民医院耳鼻咽喉头颈外科,广西百色533000 [3]百色市人民医院病理科,广西百色533000

出　　处：《现代肿瘤医学》2023年第8期1440-1447,共8页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:82060190);广西卫健委科研课题(编号:Z20211109);广西科技基地和人才专项(编号:桂科AD20297069)。

摘　　要：目的:通过生物信息学分析的方法,探讨异常纺锤体样小头畸形相关蛋白(abnormal spindle-like microcephaly-associated protein,ASPM)在鼻咽癌中的分子功能及作用机制;通过细胞实验,初步验证ASPM在鼻咽癌细胞中的作用。方法:使用R语言的limma包对鼻咽癌的芯片数据集进行基因差异表达分析;使用R语言的clusterProfiler包进行ASPM相关基因的富集分析;通过流式细胞术、CCK8实验、实时定量PCR及蛋白免疫印迹等方法,研究沉默ASPM表达对鼻咽癌细胞周期及细胞增殖的影响。结果:差异表达分析发现ASPM mRNA水平在鼻咽癌数据集中高表达(P<0.001);基因富集分析发现与ASPM相关的基因在鼻咽癌中与细胞周期、DNA复制等信号通路关联;细胞功能实验发现沉默ASPM的表达,鼻咽癌细胞周期停滞于G 1期,鼻咽癌细胞增殖减少;沉默ASPM的表达可以影响鼻咽癌细胞周期及增殖标志物的表达。结论:ASPM可能通过调控鼻咽癌细胞周期及DNA复制等信号通路,导致肿瘤发生与进展;沉默鼻咽癌细胞中ASPM mRNA的表达,可以使细胞周期停滞于G 1期,细胞增殖减少;ASPM可能作为改善鼻咽癌预后的潜在靶点。Objective:To explore the molecular function and mechanism of abnormal spindle-like microcephaly-associated protein(ASPM)in nasopharyngeal carcinoma by means of bioinformatics analysis,and to preliminarily verify the role of ASPM in nasopharyngeal carcinoma through cell experiments.Methods:Using the limma package of R language to analyze the gene differential expression of the nasopharyngeal carcinoma microarray data set.Using the clusterProfiler package of R language to conduct the enrichment analysis of ASPM-related genes.Flow cytometry,CCK8 experiment,real-time quantitative PCR and Western blotting and other methods were used to study the effect of silencing ASPM expression on the cycle and cell proliferation of nasopharyngeal carcinoma cells.Results:Differential expression analysis found that ASPM mRNA level was highly expressed in the nasopharyngeal carcinoma dataset(P<0.001).Gene enrichment analysis found that ASPM-related genes were associated with cell cycle,DNA replication and other signaling pathways in nasopharyngeal carcinoma.The cell function experiments found that the nasopharyngeal cancer cell cycle was arrested in the G 1 phase,and the proliferation of nasopharyngeal cancer cells was reduced by silencing the expression of ASPM.Silencing the expression of ASPM can affect the expression of nasopharyngeal carcinoma cell cycle and proliferation markers.Conclusion:ASPM may lead to tumorigenesis and progression by regulating signal pathways such as the cycle and DNA replication of nasopharyngeal carcinoma cells.Silencing the expression of ASPM mRNA in nasopharyngeal carcinoma cells can arrest the cell cycle in G 1 phase and reduce cell proliferation.ASPM may serve as a potential target for improving prognosis of nasopharyngeal carcinoma.

关 键 词：鼻咽癌 ASPM 富集分析 细胞周期 细胞增殖 

分 类 号：R739.63[医药卫生—肿瘤]