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目的 :研究结直肠癌中p53与组蛋白去乙酰化酶2(histone deacetylase 2,HDAC2)表达的相关性及其调控关系。方法:利用美国癌症基因组图谱计划(the Cancer Genome Atlas,TCGA)结直肠癌临床样本数据,分析p53与HDAC2表达的相关性。采用蛋白质印迹法检测HDAC2在野生型(wild type,WT)及p 53基因敲除型(p53-/-)结直肠癌HCT116细胞系中的表达情况。采用腺病毒感染技术恢复HCT116p53-/-细胞中p53的表达,然后再用蛋白质印迹法检测HDAC2表达的变化。进一步利用TCGA结直肠癌数据,分析HDAC2与p53信号通路相关基因的相关性。结果:TCGA大数据分析发现,在382例结直肠癌组织的RNA测序标本中,p53与HDAC2转录水平呈现明显的正相关性(r=0.198,P=0.000 1)。体外细胞系检测结果显示,p 53基因敲除的结直肠癌HCT116 p53-/-细胞中HDAC2蛋白的表达水平明显低于p53野生型的HCT116 WT细胞(P<0.000 1);而将重组腺病毒Ad-p53感染HCT116 p53-/-细胞后,p53和HDAC2蛋白表达水平均重新上调(P值均<0.000 1)。TCGA结直肠癌大数据分析发现,HDAC2与9个p53信号通路相关基因具有显著的同现趋势(P值均<0.05)及正相关性(P值均<0.01)。结论:结直肠癌中p53对HDAC2表达可能发挥重要的调控作用。HDAC2可能作为p53的一个下游调控蛋白,参与p53信号转导,从而在肿瘤的发生和发展进程中发挥重要作用。
Objective: To investigate the relationship between the expression of p53 and histone deacetylase 2 (HDAC2) in colorectal cancer and its regulation. Methods: The clinical data of colorectal cancer from the Cancer Genome Atlas (TCGA) were used to analyze the relationship between p53 and HDAC2 expression. The expression of HDAC2 in wild type (WT) and p53 knockout (p53 - / -) colorectal cancer HCT116 cell lines was detected by Western blotting. The adenovirus infection technique was used to restore the expression of p53 in HCT116p53 - / - cells. The expression of HDAC2 was detected by Western blotting. Further use of TCGA colorectal cancer data, analysis of HDAC2 and p53 signaling pathway related gene relevance. Results: In the TCGA large data analysis, there was a significant positive correlation between p53 and HDAC2 transcription (r = 0.198, P = 0.0001) in 382 colorectal cancer RNA sequencing samples. The results of in vitro cell lines showed that the expression level of HDAC2 protein in p53-knockout colorectal cancer HCT116 p53 - / - cells was significantly lower than that in p53 wild type HCT116 WT cells (P <0.0001), while the recombinant adenovirus P53 and HDAC2 protein levels were up-regulated again after HCT116 p53 - / - cells were infected with Ad-p53 (all P <0.000 1). Large data analysis of TCGA colorectal cancer showed that there was a significant co-occurrence trend between HDAC2 and nine p53 signaling pathways (P <0.05) and positive correlation (P <0.01). Conclusion: p53 may play an important regulatory role in the expression of HDAC2 in colorectal cancer. As a downstream regulatory protein of p53, HDAC2 is involved in p53 signal transduction and plays an important role in tumorigenesis and progression.