朱海珍1,2,3?覮,陈瑾文1,2,3,许艳1,2,3,薛斌斌1,2,3,王鑫涛1,2,3, 邓日林1,2,3,田仁云1,2,3,陈生稳1,2,3,王静静1,2,3,黄湘1,2,3.USP18促进溶瘤病毒诱导的肝癌细胞凋亡机制[J].湖南大学学报:自然科学版,2019,(6):88~95
USP18促进溶瘤病毒诱导的肝癌细胞凋亡机制
USP18 Promotes Apoptosis of Liver Cancer Cells Induced by NDV
  
DOI:
中文关键词:  线粒体  肝癌细胞  USP18  NDV  细胞凋亡  Bax  NOXA  ISG12a
英文关键词:mitochondria  liver cancer cell  USP18  NDV  cell apoptosis  mitochondria  Bax  NOXA  ISG12a
基金项目:
作者单位
朱海珍1,2,3?覮,陈瑾文1,2,3,许艳1,2,3,薛斌斌1,2,3,王鑫涛1,2,3, 邓日林1,2,3,田仁云1,2,3,陈生稳1,2,3,王静静1,2,3,黄湘1,2,3 (1.湖南大学 生物学院湖南 长沙 410082 2.湖南大学 病原生物学免疫学研究所湖南 长沙 410082
3.湖南大学 化学生物传感与计量学国家重点实验室
湖南 长沙 410082) 
摘要点击次数: 24
全文下载次数: 26
中文摘要:
      NDV感染肝癌细胞后,能够诱导细胞的凋亡,在NDV感染肝癌细胞Huh7之后,能够诱导一种去泛素化酶USP18的表达显著上调. 为了探究USP18在NDV诱导的肝癌细胞的凋亡过程中起什么作用,以肝癌细胞系Huh7为实验体系,以western blot蛋白免疫印迹和定量PCR为主要方法. 在细胞中过表达USP18,发现其能够明显促进肝癌细胞的凋亡,这表明USP18具有抗癌的功能.反之,敲低细胞中USP18的表达水平,能够有效地抑制NDV诱导的肝癌细胞凋亡.进一步揭示了USP18促进NDV诱导的细胞凋亡的机制,USP18上调了定位于线粒体上的Bax的蛋白水平,Bax能与Bak在线粒体外膜上形成孔道,增加线粒体外膜的通透性,从而促进凋亡蛋白细胞色素C的释放.同时,USP18还能诱导NOXA切割效应凋亡蛋白Caspase-7,进一步促进细胞凋亡.此外,USP18上调干扰素刺激基因ISG12a(IFN-stimulated gene 12a)的蛋白水平,抑制ISG12a的泛素化降解,这也是从另一个角度解释了其促进凋亡作用.
英文摘要:
      After NDV infects the liver tumour cell,USP18 (Ubiquitin Specific Protease 18) acts as a deubiquitin enzyme and cleaves ubiquitin from ubiquitinated protein substrates. NDV infection of liver tumour cell can induce the apoptosis of cancer cells. Infection with NDV up-regulates the expression of USP18,and the role of USP18 in the apoptosis induced by NDV was investigated. In this study, the liver tumour cell line Huh7 is taken as the system, and western blot and qualitative PCR are considered. It is found that USP18 promotes the apoptosis of cancer cells induced by NDV,which demonstrates that USP18 has the anticancer function. In contrast, knock-down of USP18 inhibits the apoptosis of the cancer cells, which reveals that USP18 can positively regulate the protein level of Bax and NOXA. Consistently,overexpression of USP18 enhances the permeability of mitochondrial membrane and promotes the release of CYTOCHROME C. Similarly, overexpression of USP18 increases the cleaved caspase-7 and strengthens the apoptosis as well. It is also found that USP18 can upregulate the protein level of ISG12a(IFN-stimulated gene 12a). It attenuates the ubiquitination degradation of ISG12a. The findings in this research provide a profound influence and a new insight towards treatment for liver cancer.
查看全文  查看/发表评论  下载PDF阅读器
关闭