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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

生长抑制剂 4 (ING4) 通过核因子 Kappa-B (NF-kB)/DNA 甲基转移酶 1 (DNMT1) 轴介导的醛脱氢酶 1A2 (ALDH1A2) 调节在口腔鳞状细胞癌中发挥肿瘤抑制作用

卷 22, 期 9, 2022

发表于: 30 June, 2022

页: [771 - 783] 页: 13

弟呕挨: 10.2174/1568009622666220406104732

价格: $65

摘要

背景：据报道，头颈部鳞状细胞癌 (HNSC) 组织中生长抑制剂 4 (ING4) 水平降低，然而，尚不清楚 ING4 是否以及如何参与调节口腔鳞状细胞癌 (OSCC) 的发展。目的：本研究旨在探讨ING4在OSCC中的作用和机制。 方法：在两种OSCC细胞系中，ING4被强制上调或下调，并在体外研究其对OSCC细胞恶性行为的影响。通过免疫共沉淀测量 ING4 上调细胞中 NF-kB p65 的泛素化水平。此外，通过甲基化特异性聚合酶链反应（MSP）测定评估了ING4对ALDH1A2甲基化水平的影响。在裸鼠中观察到ING4在体内OSCC生长中的作用。 结果：我们的结果表明，ING4在OSCC细胞系中的表达低于正常口腔角质形成细胞中的表达。在体外，ING4 过表达抑制 OSCC 细胞系的增殖、迁移和侵袭，而 ING4 沉默表现出相反的结果。我们还证明了 ING4 过表达促进了 P65 的泛素化和降解，并降低了 DNA 甲基转移酶 1 (DNMT1) 的表达和醛脱氢酶 1A2 (ALDH1A2) 的甲基化。此外，p65 的过表达挽救了由 ING4 过表达诱导的恶性行为的抑制。此外，ING4 负向调节体内 OSCC 异种移植肿瘤的生长。 结论：我们的数据证明 ING4 通过 NF-κB/DNMT1/ALDH1A2 轴在体内和体外在 OSCC 中发挥肿瘤抑制作用。

关键词: NG4、NF-κB/P65、DNMT1、ALDH1A2、口腔鳞状细胞癌、恶性表型。

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