摘要
目的探讨转录活化因子4(ATF4)对肝癌细胞(HCC)增殖、迁移、凋亡的影响及其作用机制。方法通过RNA干扰技术下调HepG2和Huh7细胞中ATF4和己糖激酶结构域成分1(HKDC1)的蛋白表达;分别用CCK-8法、克隆形成实验、划痕实验及流式细胞术检测转染后的HCC增殖、迁移及凋亡的变化,用Western blot测定肝癌细胞系中ATF4、HKDC1以及凋亡相关蛋白Bcl-2和Bax的表达情况。结果敲低ATF4、HKDC1可降低HepG2和Huh7细胞的增殖及迁移能力,并诱导其凋亡增加;敲低ATF4可抑制HepG2和Huh7细胞中HKDC1蛋白的表达。结论ATF4可能通过调节HKDC1蛋白的表达在肝癌的进展中发挥作用,HKDC1可能是肝癌治疗干预的潜在靶点。
Objective To explore the influences of activating transcription factor 4(ATF4)on the proliferation,migration and apoptosis of hepatocellular carcinoma(HCC)and itsmolecular mechanism.Methods Expression of ATF4 andthe hexokinase domain component 1(HKDC1)were down-regulated in HepG2 and Huh7 cells by RNA interference technique.In HCC cell lines,CCK-8,clone formation,wound-healing assay and flow cytometry apoptotic analysis were used to observe the changes in the proliferation,migration and apoptosis of HCC after transfection,and the expressions of ATF4,HKDC1 and apoptosis-related proteins Bcl-2 and Bax in hepatocellular carcinoma cells were determined by Western blot.Results Functional studies had shown that knockdown of ATF4 and HKDC1 not only led to an increase in cell apoptosis and a decrease in cell proliferation but also inhibited the cells′abilities of migration;ATF4 silencing could inhibit the expression of HKDC1 protein.Conclusion ATF4 may play a role in the progression of hepatocellular carcinoma by regulating the expression of HKDC1 protein,and HKDC1 may be a potential target of therapeutic intervention for HCC.
作者
张黎
崔杰
王安琪
孙国平
Zhang Li;Cui Jie;Wang Anqi(Dept of Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)
出处
《安徽医科大学学报》
CAS
北大核心
2021年第12期1932-1938,共7页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81872047)。
关键词
ATF4
HKDC1
肝细胞癌
内质网应激
ATF4
HKDC1
hepatocellular carcinoma
endoplasmic reticulum stress
