外泌体微小RNA-877-5p通过调控Nrf2/HO-1轴诱导铁死亡对肝癌细胞的影响  

Effect of Exosome miR-877-5p on Hepatocellular Carcinoma Cells Induced by Iron Mediated Cell Death Through Regulation of the Nrf2/HO-1 Axis

作　　者：王雨[1] 王楠[2] 朱姗姗 慕喜喜 曲长君 刘媛媛 Wang Yu;Wang Nan;Zhu Shanshan;Mu Xixi;Qu Changjun;Liu Yuanyuan(Department of Gastroenterology,Xi'an Central Hospital,Xi'an 710000,China;Department of Infectious Diseases,Xi'an Central Hospital,Xi'an 710000,China;Department of General Surgery,Xi'an Central Hospital,Xi'an 710000,China;Department of Radiology,Xi'an Central Hospital,Xi'an 710000,China)

机构地区：[1]西安市中心医院消化科,西安710000 [2]西安市中心医院感染科,西安710000 [3]西安市中心医院普外科,西安710000 [4]西安市中心医院放射科,西安710000

出　　处：《成都医学院学报》2024年第4期568-572,共5页Journal of Chengdu Medical College

基　　金：陕西省科学技术厅重点研发计划项目(No:2023-YBSF-050)。

摘　　要：目的分析外泌体微小RNA-877-5p(miR-877-5p)通过调控转录因子NF-E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)轴诱导铁死亡对肝癌细胞增殖、凋亡的影响。方法检测正常肝细胞与肝癌细胞株中miR-877-5p表达量,并对MHCC97H细胞进行转染,分为空白组、miR-877-5p抑制剂组、miR-877-5p模拟物组,检测各组铁死亡相关因子Nrf2、HO-1表达量,观察并分析各组MHCC97H细胞增殖、侵袭、迁移、凋亡情况。结果与正常肝细胞L02相比,肝癌细胞株中HEP3B、HCCLM3、HepG2、MHCC97H mRNA表达量降低(P<0.05);与肝癌细胞HEP3B、HCCLM3、HepG2相比,肝癌细胞MHCC97H mRNA表达量降低(P<0.05);与空白组相比,miR-877-5p抑制剂组miR-877-5p mRNA表达量、细胞凋亡率降低(P<0.05),溶质载体家族7成员11(SLC7A11)和谷胱甘肽过氧化物酶4(GPX4)的表达量、增殖活性、迁移细胞数、侵袭细胞数及Nrf2、HO-1表达量升高(P<0.05),miR-877-5p模拟物组miR-877-5p mRNA表达量、细胞凋亡率升高(P<0.05),SLC7A11、GPX4的表达量、增殖活性、迁移细胞数、侵袭细胞数及Nrf2、HO-1表达量降低(P<0.05);与miR-877-5p抑制剂组相比,miR-877-5p模拟物组miR-877-5p mRNA表达量、细胞凋亡率升高(P<0.05),SLC7A11、GPX4的表达量、增殖活性、迁移细胞数、侵袭细胞数及Nrf2、HO-1的表达量降低(P<0.05)。结论上调外泌体miR-877-5p可抑制Nrf2/HO-1轴的激活,促使铁死亡,抑制肝癌细胞增殖,加快癌细胞的凋亡速度。Objective To analyze the effect of exosome microRNA-877-5p(miR-877-5p)on the proliferation and apoptosis of hepatocellular carcinoma(HCC)cells by regulating the transcription factor NF-E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)axis to induce ferroptosis.Methods Detect the expression level of miR-877-5p in normal liver cells and HCC cell lines.Transfect MHCC97H cells into blank group,miR-877-5p inhibitor group,and miR-877-5p mimetic group.Detect the expression level of iron death related factors Nrf2 and HO-1 in each group.And observe the proliferation,invasion,migration,and apoptosis of cells in each group.Results Compared with normal liver cell L02,HCC cells HEP3B,HCCLM3,HepG2,and MHCC97H showed a decrease in the expression level of miR-877-5p mRNA(P<0.05).Compared with HCC cells HEP3B,HCCLM3,and HepG2,HCC cell MHCC97H showed a decrease in the expression level of miR-877-5p mRNA(P<0.05).Compared with the blank group,the miR-877-5p inhibitor group exhibited decreased miR-877-5p mRNA expression and cell apoptosis rate(P<0.05),but increased solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)expression,proliferation activity,number of migrating cells,number of invading cells,and Nrf2 and HO-1 expression levels(P<0.05),the miR-877-5p mimetic group exhibited increased miR-877-5p mRNA expression and cell apoptosis rate(P<0.05),but decreased SLC7A11 and GPX4 expression levels,proliferation activity,number of migrating cells,number of invading cells,and Nrf2 and HO-1 expression levels(P<0.05).Compared with the miR-877-5p inhibitor group,the miR-877-5p mimetic group showed an increase in miR-877-5p mRNA expression and cell apoptosis rate(P<0.05),but a decrease in SLC7A11 and GPX4 expression levels,proliferation activity,number of migrating cells,number of invading cells,and Nrf2 and HO-1 expression levels(P<0.05).Conclusion Upregulation of exosome miR-877-5p can inhibit Nrf2/HO-1 axis activation,promote ferroptosis,inhibit HCC cell proliferation,and accelerate the apoptosis rate of HCC cells

关 键 词：肝癌 外泌体 微小RNA-877-5p 增殖 凋亡 

分 类 号：R735[医药卫生—肿瘤]