Hypoxia-induced nuclear translocation of ACO2 promotes the proliferation and migration of hepatocellular carcinoma PLC/PRF/5 cells

Li Yunying1; Li Jing1; Wan Yuanyuan1; He Jiaming1; Chen An1; Ma Jing1; Wang Huimin1; Chen Dilong1, 2

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Hypoxia-induced nuclear translocation of ACO2 promotes the proliferation and migration of hepatocellular carcinoma PLC/PRF/5 cells

VernacularTitle:低氧诱导乌头酸酶2入核促进肝细胞癌PLC/PRF/5细胞的增殖和迁移
Author: Li Yunying1 ^{1
,

2} ; Li Jing1 ^{1
,

2} ; Wan Yuanyuan1 ^{1
,

2} ; He Jiaming1 ^{1
,

2} ; Chen An1 ^{1
,

2} ; Ma Jing1 ^{1
,

2} ; Wang Huimin1 ^{1
,

2} ; Chen Dilong1, 2 ^{1
,

2}
Author Information

1. Department of Histology and Embryology, School of Basic Medical Sciences, Chongqing Key Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China;
2. Key Laboratory of Quality Monitoring for Narcotic and Psychotropic Drugs of the National Medical Products Administration, Chongqing Institute for Food and Drug Control, Chongqing Municipal Drug Administration, Chongqing 401121, China
Publication Type:Journal Article
Keywords: 乌头酸酶2；肝细胞癌；PLC/PRF/5；低氧；增殖；迁移；侵袭
From: Chinese Journal of Cancer Biotherapy 2026;33(8):840-847
CountryChina
Language:Chinese
Abstract: [摘要] 目的：探究乌头酸酶2（ACO2）发生核转位的条件和作用机制并探讨ACO2核转位对肝癌细胞PLC/PRF/5增殖、迁移和侵袭的影响。方法：借助Human Protein Atlas（HPA）数据库分析ACO2在人肝癌组织中的表达与亚细胞定位；利用NLStradamus网站预测ACO2的潜在核定位信号（NLS），并通过基因截短技术构建NLS缺失的ACO2基因（ACO2 ∆NLS）；将野生型（ACO2WT）及突变型（ACO2ΔNLS）质粒转染至人肝癌PLC/PRF/5细胞，分别在常氧及低氧（1% O₂）条件下培养；采用免疫荧光染色技术，分析低氧条件影响ACO2入核的机制；通过EdU染色、划痕实验及Transwell实验评估PLC/PRF/5细胞的增殖、迁移与侵袭能力；借助WB检测胞核和胞质中ACO2的表达水平以及迁移、侵袭相关蛋白MMP2与MMP9表达水平的变化。结果：HPA数据库分析显示，ACO2在肝癌细胞的细胞核和细胞质中均呈高表达；免疫荧光染色和WB结果显示，低氧能够以NLS依赖的方式显著诱导ACO2发生核转位（均P < 0.01）；功能学实验显示，低氧诱导的ACO2核转位能进一步显著促进PLC/PRF/5细胞的增殖、迁移（均P < 0.05）和侵袭（均P < 0.05）能力。WB实验表明，ACO2核转位可上调迁移、侵袭相关蛋白MMP2与MMP9的表达水平（均P < 0.05）。结论：低氧能以NLS依赖的方式诱导ACO2发生核转位，从而增强PLC/PRF/5细胞的增殖、迁移和侵袭能力。
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