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基因沉默伴侣蛋白CCT6A对甲状腺未分化癌细胞增殖和侵袭能力的影响
作者:孙骥1 2  崔文娟3  李敬东1 2  唐涛1 2 
单位:1. 川北医学院附属医院 肝胆外科, 四川 南充 637000;
2. 川北医学院 肝胆胰肠研究所, 四川 南充 637000;
3. 遂宁市中心医院 神经中心三病区, 四川 遂宁 629000
关键词:分子伴侣蛋白 CCT6A 甲状腺未分化癌 SMAD2 细胞增殖 细胞侵袭 
分类号:R73-35
出版年·卷·期(页码):2021·49·第七期(719-724)
摘要:

目的:探讨基因沉默伴侣蛋白CCT6A对甲状腺未分化癌细胞(8505C和CAL-62)增殖和侵袭能力的影响。方法:比较人新鲜甲状腺癌癌旁组织、甲状腺乳头状癌组织、甲状腺未分化癌组织中CCT6A mRNA相对表达量;选择两种人甲状腺未分化癌细胞株8505C和CAL-62,构建敲低CCT6A蛋白表达水平的细胞系,利用蛋白质印迹法验证转染效率后检测信号转导蛋白SMAD2的表达和活化。CCK8实验检测敲低CCT6A表达后甲状腺未分化癌细胞增殖能力的变化,Transwell实验检测细胞的迁移能力。结果:甲状腺未分化癌组织中CCT6A的mRNA表达水平上调。敲低CCT6A的甲状腺未分化癌细胞8505C和CAL-62中信号转导蛋白SMAD2的磷酸化激活水平显著下调。与阴性对照组相比,基因沉默实验组的细胞增殖能力显著下降,其侵袭能力亦显著减弱(P<0.05)。结论: CCT6A在甲状腺未分化癌发生发展中起关键作用,敲低CCT6A可通过下调SMAD2活化水平抑制细胞增殖和侵袭能力,未来CCT6A可能成为治疗甲状腺未分化癌的潜在靶点。

Objective: To investigate the effects of CCT6A on proliferation and invasion of anaplastic thyroid cancer cells (8505C and CAL-62). Methods: Fresh human paracancerous tissue,papillary thyroid cancer tissue and anaplastic thyroid cancer tissue was collected to measure the relative expression of CCT6AmRNA. Two anaplastic thyroid cancer cell lines (8505C and CAL-62) were transfected to knockdown CCT6A protein expression. The transfection efficiency was verified by Western blot, the expression and phosphorylation activation of signal transduction protein SMAD2 were detected. CCK8 assay was performed to detect proliferation ability of anaplastic thyroid cancer cells after CCT6A downregulation, and transwell assay was used to detect the migration ability of 8505C and CAL-62 cells.Results: Compared with paracanceroustissues and papillary thyroid carcinoma tissues, the expressionof CCT6A mRNAin anaplastic thyroid cancer tissues was significantly higher. The phosphorylation and activation of signal transduction protein SMAD2 were significantly downregulated in 8505C and CAL-62 cells with CCT6A knockdown. Compared with the negative control group, the proliferationand invasion ability of cells in sh-CCT6A group were significantly decreased(P< 0.05).Conclusion: CCT6A plays a key role in the development and progression of anaplastic thyroid cancer. CCT6A knockdown can inhibit cell proliferation and invasion by suppressing the activation level of SMAD2. CCT6A may become a potential target for anaplastic thyroid cancer therapy.

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