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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

CTTN和FGF2联合RNAi通过Ras/ERK信号通路调控肝癌细胞迁移、侵袭及G1/S转变

卷 24, 期 8, 2024

发表于: 29 November, 2023

页: [791 - 803] 页: 13

弟呕挨: 10.2174/0115680096254722231025110912

价格: $65

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摘要

背景：大多数肝细胞癌(HCC)患者死于快速进展和远处转移。基因治疗是HCC治疗的一个很有前途的选择，但有效的靶向方法仍然有限。 目的：CTTN/ contactn在肌动蛋白聚合和调节细胞骨架重塑中起关键作用。然而，CTTN在HCC中的相互作用网络尚不清楚。 方法：siRNA被设计用于CTTN沉默，Affymetrix基因芯片测序获得HCC细胞系SMMC-7721中CTTN敲除后的基因谱。利用qRT-PCR技术鉴定CTTN可能的相互作用基因。检测CTTN和成纤维细胞生长因子2 (FGF2)联合RNA干扰(RNAi)对HCC的抑制作用。 结果：共筛选出1717个显著改变基因，鉴定出12个潜在的CTTN相互作用基因。验证了CTTN与FGF2的相互作用，CTTN与FGF2的联合RNAi实现了协同效应，比单独敲除CTTN或FGF2更能抑制HCC细胞的迁移、侵袭和G1/S转变。机制上，CTTN和FGF2的联合RNAi调节了Ras/ERK信号通路。此外，CTTN和FGF2联合RNAi后，EMT上皮标志物E-cadherin上调，间质标志物Vimentin和细胞周期蛋白Cyclin D1下调。此外，qRT-PCR和免疫组化染色显示，CTTN和FGF2在转移性HCC组织中均高表达。 结论：CTTN和FGF2的联合RNAi可能是一种新的、有前途的HCC侵袭转移干预策略。

关键词: CTTN, FGF2，迁移，侵袭，G1/S转换，Ras/ERK。

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