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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

HOTAIR竞争性地将MiRNA330结合为分子海绵，以增加胃癌对曲妥珠单抗的耐药性

卷 20, 期 9, 2020

页: [700 - 709] 页: 10

弟呕挨: 10.2174/1568009620666200504114000

价格: $65

摘要

背景：HOTAIR是在肿瘤中研究最广泛的长非编码RNA之一，与肿瘤的增殖，迁移，侵袭和化学耐药性密切相关。 目的：在这里，我们研究了增殖和化学抗性过程的机制。 方法：从接受胃癌手术切除并接受曲妥珠单抗治疗的患者中收集总共75份样品。分离并培养原代细胞。我们还通过构建慢病毒载体开发了过表达HOTAIR的细胞系。使用一系列已建立的生物分子方法研究了这些细胞系。 结果：我们发现，HOTAIR水平与胃癌对曲妥珠单抗的敏感性呈负相关，并且HOTAIR的过表达可以促进胃癌细胞的增殖和侵袭。细胞过度表达HOTAIR对两种不同类型的人类表皮生长因子受体2（HER2）抑制剂（曲妥珠单抗和afatinib）的敏感性表明，HOTAIR的过度表达对曲妥珠单抗具有特异性。此外，荧光素酶报告基因分析和蛋白质印迹分析表明，存在一个以miRNA330为核心的HOTAIR-miRNA330-ERBB4竞争性内源RNA调节网络。 结论：HOTAIR不仅可以促进肿瘤的增殖，而且可以增强肿瘤细胞对药物的耐药性。我们的实验数据不仅显示了HOTAIR在胃癌中的强表达，而且还表明HOTAIR的强表达引起胃癌细胞对曲妥珠单抗的敏感性，为术后药物治疗提供了有用的参考。

关键词: 曲妥珠单抗，HOTAIR，阿法替尼，ERBB4，HER2，miRNA330，胃癌。

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