Page 26 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第41卷第8期
·1128 · Journal of Nanjing Medical University（Natural Sciences） 2021年8月

·基础医学·

抑制PP2Acα促进胃癌进展中WTAP高表达

程照翔 ，方 超 ，吕纯业 1*
2*
1
南京医科大学附属江宁医院普通外科，中心实验室，江苏 南京 211100
1 2

［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 tran⁃
scription 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⁃mesen⁃
chymal 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。
［关键词］ 胃癌；PP2Acɑ；PPP2CA；WTAP
［中图分类号］ R735.2 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）08⁃1128⁃07
doi：10.7655/NYDXBNS20210804

WTAP levels are upregulated in the progression of gastric cancer by inhibiting PP2Acα

1
2*
CHENG Zhaoxiang ，FANG Chao ，LÜ Chunye 1*
1 Department of General Surgery，Department of Central Laboratory，the Affiliated Jiangning Hospital of Nanjing
2
Medical University，Nanjing 211100，China

［Abstract］ 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.
［Key words］ gastric cancer；PP2Acɑ；PPP2CA；WTAP
［J Nanjing Med Univ，2021，41（08）：1128⁃1134］

［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）
∗
通信作者（Corresponding author），E⁃mail：fangchaonjmu@hotmail.com；chunyel@163.com