结直肠癌中p53对组蛋白去乙酰化酶2表达的调控作用  

P53 regulates the expression of histone deacetylase 2 in colorectal cancer

作　　者：刘健[1] 李春晓 雷箴[1] 袁雯 温韬[1] 钱海利 

机构地区：[1]首都医科大学附属北京朝阳医院医学研究中心,北京100020 [2]国家癌症中心/中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室,北京100021

出　　处：《肿瘤》2017年第10期1017-1023,共7页Tumor

基　　金：国家自然科学基金资助项目(编号:81502384)~~

摘　　要：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 study the correlation between the expressions of p53 and histone deacetylase 2 （HDAC2） in colorectal cancer, and to explore their regulative relationship. Methods： The association between p53 and HDAC2 mRNAs was explored by the Cancer Genome Atlas （TCGA） clinical colorectal cancer data analysis. The expression of HDAC2 in wide-type （WT） and p53-knockout （p53-^-） colorectal HCT116 cell lines was detected by Western blotting. After p53 expression in HCT116 p53-j- cells was recovered by adenovirus infection method, the expression of HDAC2 was detected by Western blotting again. Then TCGA colorectal cancer data were further used to analyze the relationship between HDAC2 and p53 signaling pathway-related genes. Results： TCGA data analysis showed that the transcriptional level of p53 was positively correlated with HDAC2 in 382 RNA-sequencing specimens of colorectal cancer （r = 0.198, P = 0.000 1）. As compared with HCT116 WT cells, the expression level of HDAC2 protein was significantly reduced in HCT116 p53-j cells （P 〈 0.000 1）. After infection with Ad-p53 adenovirus, the expression levels of p53 and HDAC2 proteins in HCT116 p53-j cells were recovered （both P 〈 0.000 1）. Further analysis of TCGA colorectal cancer data showed that there was significant co-occurrence （all P 〈 0.05） and positive association （all P 〈 0.01） between the expressions of HDAC2 and nine p53 signaling pathway-related genes. Conclusion： P53 may play an important role in regulating HDAC2 expression in colorecta cancer. HDAC2 may act as a down-stream regulator of p53, participate in p53 signa transduction, and modulate tumorigenesis and progression.

关 键 词：结直肠肿瘤 基因表达调控 基因 p53 组蛋白脱乙酰基酶类 

分 类 号：R735.34[医药卫生—肿瘤]