| 逯 越,王万里,宋巧炎.去泛素化酶USP33对胃癌上皮细胞-间质转化的影响及对癌细胞迁移、侵袭的作用[J].肿瘤学杂志,2022,28(4):272-279. |
| 去泛素化酶USP33对胃癌上皮细胞-间质转化的影响及对癌细胞迁移、侵袭的作用 |
| Effect of Deubiquitinating Enzyme USP33 on Epithelial-mesen-chymal Transition， Migration and Invasion of Gastric Cancer Cells |
| 投稿时间：2021-09-01 |
| DOI：10.11735/j.issn.1671-170X.2022.04.B004 |
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| 中文关键词: 胃癌 USP33 转化生长因子-β信号通路 上皮细胞-间质转化 迁移 侵袭 |
| 英文关键词:gastric cancer USP33 transforming growth factor-β signaling pathway epithelial-mesenchymal transition migration invasion |
| 基金项目:河南省科技发展计划（162300410101） |
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| 中文摘要: |
| 摘 要：［目的］ 观察去泛素化酶USP33对胃癌上皮细胞-间质转化（epithelial-mesenchymal transition，EMT）及细胞迁移侵袭能力的影响，并探究其作用机制。［方法］ qRT-PCR法检测胃癌上皮细胞MGC-803、SGC-7901和人胃黏膜上皮细胞GES-1中去泛素化酶USP33的表达。MGC-803和SGC-7901细胞转染USP33-siRNA沉默USP33基因表达，qRT-PCR检测沉默效率，使用转化生长因子-β（transforming growth factor-β，TGF-β）信号通路抑制剂SB431542处理沉默USP33后的MGC-803和SGC-7901细胞，MTT法检测细胞增殖能力，划痕实验检测细胞迁移能力，Transwell实验检测细胞侵袭能力，Western blot法检测细胞E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）、波形蛋白（Vimentin）、TGF-β、Smad2和α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）的表达水平。［结果］ qRT-PCR检测结果显示，与GES-1细胞比较，MGC-803、SGC-7901细胞中USP33表达水平显著性降低。MTT实验、划痕实验和Transwell实验检测结果显示，USP33基因敲低后，MGC-803、SGC-7901细胞的增殖、迁移和侵袭能力显著性提高。Western blot检测结果显示，沉默USP33可使MGC-803和SGC-7901细胞E-cadherin表达降低，N-cadherin、Vimentin、TGF-β、Smad2和α-SMA表达升高，而TGF-β抑制剂SB431542则逆转了这一现象，上述指标差异均有统计学意义（P＜0.05）。［结论］ USP33能够抑制胃癌细胞增殖、迁移、侵袭及EMT转化，沉默USP33可增加其增殖、迁移和侵袭能力并促进EMT转化过程，其作用机制与抑制TGF-β信号通路的活化有关。 |
| 英文摘要: |
| Abstract： ［Objective］ To investigate the effect of deubiquitinating enzyme USP33 on epithelial-mesenchymal transition(EMT)， migration， invasion of gastric cancer cells and its mechanism. ［Methods］ The expression of deubiquitinating enzyme USP33 was detected with qRT-PCR in gastric cancer MGC-803， SGC-7901 cells and human gastric mucosal GES-1 epithelial cells. MGC-803 and SGC-7901 cells were transfected with USP33-siRNA to silence USP33 gene expression， and the silencing efficiency was determined with qRT-PCR. After silencing USP33， MGC-803 and SGC-7901 cells were treated with TGF-β signaling pathway inhibitor SB431542. The cell proliferation ability was detected with MTT assay， the cell migration and invasion ability was detected with scratch assay and Transwell assay. The expression levels of E-cadherin， N-cadherin， Vimentin， TGF-β， Smad2 and α-SMA were detected with Western blot. ［Results］ The expression levels of USP33 in MGC-803 and SGC-7901 cells were significantly reduced compared with GES-1 cells. The proliferation， migration and invasion ability of MGC-803 and SGC-7901 cells were significantly increased after USP33 gene knockdown. The expression of E-cadherin in MGC-803 and SGC-7901 cells was reduced after silencing USP33， while the expression of N-cadherin， Vimentin， TGF-β， Smad2 and α-SMA were increased. The TGF-β inhibitor SB431542 significantly reversed above results(P<0.05). ［Conclusion］ USP33 can inhibit the proliferation， migration， invasion and EMT transformation of gastric cancer cells. Silencing USP33 can increase the proliferation， migration and invasion ability of gastric cancer cells and promote the EMT transformation process. Its mechanism of action is related to the inhibition of the activation of TGF-β signaling pathway. |
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