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USP13抑制溶瘤病毒诱导的肝癌细胞凋亡机制 被引量:3

USP13 Restrains Apoptosis of Liver Cancer Cells Induced by NDV
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摘要 新城疫病毒(Newcastle Disease Virus,NDV)是一种复制能力较强且特异性识别并杀伤肿瘤细胞的禽类病毒.肝癌细胞被NDV感染后,会特异性激活肝癌细胞中的凋亡信号通路,诱导肝癌细胞发生凋亡.USP13(Ubiquitin Specific Protease 13)是去泛素化酶家族的一员,能够去泛素化和稳定PTEN分子.在Huh7和HLCZ01这两种肝癌细胞中感染NDV时,USP13的表达水平均明显降低.在NDV感染的Huh7和HLCZ01细胞中过表达USP13,细胞凋亡均明显受到抑制.反之,敲低细胞中USP13的水平,细胞凋亡明显得到增强.进一步揭示了USP13抑制NDV诱导肝癌细胞凋亡的机制,在两种肝癌细胞中过表达USP13虽然不影响细胞中NDV的复制,但发现USP13能够上调凋亡信号通路中的一个重要分子Bcl-2,进而抑制肝癌细胞的凋亡.USP13在NDV诱导的肝癌细胞凋亡中发挥着重要的作用,同时为肝癌的溶瘤病毒治疗提供了一个新的理论依据. Newcastle Disease Virus is an avian virus with strong replication ability,which can specifically identify and kill tumor cells.When liver cancer cells are infected with NDV,the apoptosis signaling pathway is activated,inducing apoptosis.USP13(Ubiquitin Specific Protease 13)is a member of the ubiquitination enzyme family,and deubiquitylate and stabilize PTEN.The expression of USP13 is obviously decreased when NDV infected Huh7 or HLCZ01 cells.USP13 is overexpressed in NDV-infected Huh7 or HLCZ01 cells,which significantly restrains apoptosis.Conversely,knockdown USP13 significantly enhances apoptosis.Further studies revealed the underlying mechanism that USP13 restrains NDV-induced apoptosis.Although overexpression of USP13 doesn't affect NDV replication in two types of liver cancer cells,USP13 can upregulate an important molecule Bcl-2,thereby inhibiting apoptosis.USP13 plays an important role in NDV-induced apoptosis.At the same time,a new theory basis for the oncolytic treatment of liver cancer is provided.
作者 朱海珍 黄湘 王静静 许艳 陈瑾文 王鑫涛 ZHU Haizhen;HUANG Xiang;WANG Jingjing;XU Yan;CHEN Jinwen;WANG Xintao(College of Biology,Hunan University,Changsha 410082,China;Institute of Pathogen Biology and Immunology,Hunan University,Changsha 410082,China;State Key Laboratory of Chemo/Biosensing and Chemometrics,Hunan University,Changsha 410082,China)
出处 《湖南大学学报(自然科学版)》 EI CAS CSCD 北大核心 2019年第12期107-113,共7页 Journal of Hunan University:Natural Sciences
基金 国家自然科学基金资助项目(81730064,81571985) 国家科技重大专项资助项目(2017ZX10202201)~~
关键词 USP13 NDV 肝癌 凋亡 c-PARP Bcl-2 细胞 USP13 NDV HCC apoptosis c-PARP Bcl-2 cell enzyme
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