Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress  

作　　者：Yan-Fei Li Fang-Yuan Zheng Xin-Yu Miao Hai-Long Liu Yao-Yao Zhang Nai-Xia Chao Fa-Rong Mo 

机构地区：[1]School of Basic Medical Sciences,Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China [2]Key Laboratory of Biological Molecular Medicine Research(Guangxi Medical University),Education Department of Guangxi Zhuang Autonomous Region,Nanning 530021,Guangxi Zhuang Autonomous Region,China [3]Key Laboratory of Human Development and Disease Research(Guangxi Medical University),Education Department of Guangxi Zhuang Autonomous Region,Nanning 530021,Guangxi Zhuang Autonomous Region,China

出　　处：《World Journal of Gastroenterology》2024年第19期2564-2574,共11页世界胃肠病学杂志（英文版）

基　　金：Supported by Natural Science Foundation of Guangxi Zhuang Autonomous Region,China,No.2023GXNSFAA026070 and No.2018GXNSFAA281071.

摘　　要：BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

关 键 词：Cell division cyclin 25C Hepatocellular carcinoma Endoplasmic reticulum stress PROLIFERATION Apoptosis 

分 类 号：R575.2[医药卫生—消化系统]