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

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G1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G1期,细胞增殖减少；ASPM可能作为改善鼻咽癌预后的潜在靶点。

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

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 G1 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 G1 phase and reduce cell proliferation.ASPM may serve as a potential target for improving prognosis of nasopharyngeal carcinoma.