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山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (2): 21-28.doi: 10.6040/j.issn.1671-7554.0.2019.1034

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过表达YAP基因通过PI3K/AKT/mTOR信号通路促进舌鳞癌增殖

王莹,张雅菲,文勇   

  1. 山东大学口腔医学院 口腔医院种植科, 山东省口腔生物材料与组织再生工程实验室, 〓〓〓〓山东省口腔组织再生重点实验室, 山东 济南 250012
  • 出版日期:2020-02-10 发布日期:2022-09-27
  • 通讯作者: 文勇. E-mail:wenyong@sdu.edu.cn
  • 基金资助:
    山东省自然科学基金(ZR2018MH018);山东省医药卫生科技发展计划(2017WS111);山东省博士后创新项目专项资金(201703071)

YAP gene overexpression promotes tongue squamous carcinoma growth through PI3K/AKT/mTOR signaling pathway

WANG Ying, ZHANG Yafei, WEN Yong   

  1. Department of Implantology, School and Hospital of Stomatology, Shandong University &
    Shandong Key Laboratory of Oral Tissue regeneration &
    Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, Shandong, China
  • Online:2020-02-10 Published:2022-09-27

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摘要： 目的 基于PI3K/AKT/mTOR信号通路,探究过表达YAP基因对舌鳞癌细胞增殖和凋亡的分子学调控机制。 方法 构建稳定过表达YAP基因的舌鳞癌CAL27和SCC25细胞系。采用CCK-8和流式细胞术分析过表达YAP基因对细胞增殖、周期和凋亡的影响。蛋白免疫印迹法分析过表达YAP基因对细胞内CDK4、CDK6、p21、BAX及对PI3K/AKT/mTOR信号通路的影响。 结果 CAL27细胞和SCC25细胞中过表达YAP组YAP mRNA较对照组升高(t=-19.29, P<0.001; t=-5.44, P<0.001),且过表达YAP组的YAP蛋白表达量较对照组增加(t=-31.28, P<0.001; t=-42.84, P<0.001);过表达YAP组的G1期细胞比例减少,过表达YAP组S期细胞比例较对照组升高;过表达YAP组的早期凋亡和晚期凋亡细胞都减少;过表达YAP组细胞中CDK4、CDK6、BCL-2、PARP等蛋白表达升高,p21、BAX及caspase3蛋白的表达减少;过表达YAP基因可使CAL27和SCC25细胞内AKT(tCAL27=-30.60, P<0.001; tSCC25=-16.77, P<0.001)、p-AKT(tCAL27=-10.23, P<0.001; tSCC25=-10.67, P<0.001),mTOR(tCAL27=-13.93, P<0.001; tSCC25=-9.57, P<0.001)、p-mTOR(tCAL27=-17.17, P<0.001; tSCC25=-8.51, P<0.001)表达量较对照组增高。 结论 过表达YAP基因可以通过PI3K/AKT/mTOR信号通路促进CAL27和SCC25细胞增殖并抑制细胞凋亡。

关键词: 过表达YAP基因, 舌鳞癌, 增殖, 凋亡, PI3K/AKT/mTOR信号通路

Abstract: Objective To explore the molecular mechanism of YAP gene overexpression on the proliferation and apoptosis of tongue squamous carcinoma cells through the PI3K/AKT/mTOR signaling pathway. Methods CAL27 and SCC25 cell lines overexpressing YAP gene were constructed. The effects of YAP gene overexpression on cell proliferation, cell cycle and apoptosis were detected with CCK-8 and flow cytometry. Effects of YAP gene overexpression on the CDK4, CDK6, p21, BAX and PI3K/AKT/mTOR signaling pathways were analyzed with Western blotting. Results The mRNA expression of YAP in the overexpressing group was higher than that in the control group(t=-19.29, P<0.001; t=-5.44, P<0.001), and the protein expression was also higher(t=-31.28, P<0.001; t=-42.84, P<0.001). In the overexpressing group, the proportion of cells in G1 phase decreased, while the proportion of cells in S phase 山 东 大 学 学 报 (医 学 版)58卷2期 -王莹,等.过表达YAP基因通过PI3K/AKT/mTOR信号通路促进舌鳞癌增殖 \=-increased; the numbers of both early apoptosis and late apoptosis cells reduced; the protein expressions of CDK4, CDK6, BCL-2, PARP increased, while the protein expressions of p21, BAX and caspase3 decreased. YAP gene overexpression increased the expressions of AKT(tCAL27=-30.60, P<0.001; tSCC25=-16.77, P<0.001), p-AKT(tCAL27=-10.23, P<0.001; tSCC25=-10.67, P<0.001), mTOR(tCAL27=-13.93, P<0.001; tSCC25=-9.57, P<0.001), and p-mTOR(tCAL27=-17.17, P<0.001; tSCC25=-8.51, P<0.001). Conclusion YAP gene overexpression promotes proliferation of CAL27 and SCC25 cells and inhibits apoptosis through the PI3K/AKT/mTOR signaling pathway.

Key words: YAP gene overexpression, Tongue squamous cell carcinoma, Proliferation, Apoptosis, PI3K/AKT/mTOR signaling pathway

中图分类号: 

  • R739.86
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