文章摘要
程照翔,方 超,吕纯业.抑制PP2Acα促进胃癌进展中WTAP高表达[J].南京医科大学学报,2021,(8):1128~1134
抑制PP2Acα促进胃癌进展中WTAP高表达
WTAP levels are upregulated in the progression of gastric cancer by inhibiting PP2Acα
投稿时间:2021-01-19  
DOI:doi:10.7655/NYDXBNS20210804
中文关键词: 胃癌  PP2Acɑ  PPP2CA  WTAP
英文关键词: gastric cancer  PP2Acɑ  PPP2CA  WTAP
基金项目:江苏省自然科学基金(BK20180135);江苏大学医学临床科学与技术发展基金(JLY20160176);江苏省卫健委基金(YG201305)
作者单位
程照翔 南京医科大学附属江宁医院普通外科江苏 南京 211100 
方 超 南京医科大学附属江宁医院中心实验室江苏 南京 211100 
吕纯业 南京医科大学附属江宁医院普通外科江苏 南京 211100 
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中文摘要:
      目的:探讨蛋白磷酸酶2A催化亚基Cα(PP2Acα)的抑制是否会影响胃癌细胞的恶性表型,以及维尔姆肿瘤1相关蛋白(Wilms’ tumour 1?associating protein,WTAP)在这一进展中的表达。方法:使用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分别比较PP2Acα编码基因(PPP2CA)、WTAP基因在胃癌组织与正常胃黏膜组织中的表达量;使用KM?plot网站(http://kmplot.com/analysis/)分析PPP2CA、WTAP与胃癌预后的关系;使用慢病毒介导的短发卡RNA(short hairpin RNA,shRNA)在胃癌细胞中敲减PPP2CA,从而抑制PP2Acα的表达;随后提取RNA、蛋白分别进行定量逆转录PCR(quantitative reverse transcription PCR,RT?qPCR)、蛋白免疫印迹(Western blot),检测PPP2CA、WTAP的mRNA水平及蛋白的表达;最后在离体与活体层面观察抑制PP2Acα对于胃癌细胞恶性表型的影响。结果:抑制PP2Acα后,胃癌细胞发生上皮间质转化(epithelial?mesenchymal transition,EMT)形态改变,且增殖、迁移与侵袭能力均得到了增强,并伴随着WTAP蛋白及mRNA水平的显著升高。结论:抑制PP2Acɑ促进胃癌细胞的恶性表型,可能是通过上调WTAP的表达水平实现的。
英文摘要:
      Objective:This stndy aims to investigate whether the inhibition of protein phosphatase 2A catalytic subunit Cα(PP2Acα) affects the malignant phenotype of gastric cancer cells and the expression of Wilms tumor 1 related protein(WTAP) in this progression. Methods:The Cancer Genome Atlas(TCGA)database was used to compare the expression of PP2Acα coding gene(PPP2CA)and WTAP in gastric cancer and normal tissues adjacent to the cancer;the KM?plot website was used to analyze the relationship between PPP2CA,WTAP and the prognosis of gastric cancer;lentivirus?mediated short hair Card RNA(shRNA)was used to inhibit the expression of PP2Acα in gastric cancer cells,and then RNA and protein for PCR and WB were extracted to detect the mRNA and protein levels of PPP2CA/PP2Acα and WTAP,respecfively;finally,the influences of PP2Acα inhibition on gastric cancer cells phenotype were detected in vitro and in vivo. Results:After inhibiting PP2Acα,it was found that the proliferation,migration and invasion capabilities of gastric cancer cells were enhanced with epithelial?mesenchymal transition(EMT),accompanied by a significant increase in the protein levels of WTAP. Conclusion:Inhibition of PP2Acɑ promotes the malignant phenotype of gastric cancer cells,which may be achieved by upregulating the levels of WTAP.
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