circ-0058063对食管癌细胞铁死亡作用机制的研究  

Mechanism of circ-0058063 on ferroptosis in esophageal cancer cells

作　　者：胡东玉[1] 李慧[1] 杨东[1] 刘海英[1] 谷振芳[1] HU Dong-yu;LI Hui;YANG Dong;LIU Hai-ying;GU Zhen-fang(Department of Oncology,Affiliated Hospital of Jining Medical College,Jining Shandong 272029,China)

机构地区：[1]济宁医学院附属医院肿瘤科,山东济宁272029

出　　处：《局解手术学杂志》2025年第4期289-294,共6页Journal of Regional Anatomy and Operative Surgery

基　　金：济宁市重点研发计划项目(2022YXNS050)。

摘　　要：目的探究circ-0058063调控ERK/MAPK信号通路对食管癌细胞铁死亡的作用机制。方法将EC9706细胞随机分为Control组、si-NC组、si-circ-0058063组和si-circ-0058063+ISO组。qRT-PCR检测食管癌组织及细胞中circ-0058063表达;CCK-8和克隆形成实验检测细胞增殖能力;检测细胞中Fe^(2+)、丙二醛(MDA)、谷胱甘肽(GSH)和活性氧(ROS)水平;Western blot检测细胞中ERK/MAPK信号通路及铁死亡相关蛋白表达。结果与癌旁组织相比,食管癌组织中circ-0058063表达水平明显升高(P<0.05);人食管癌细胞EC9706中circ-0058063表达水平明显高于人正常食管上皮细胞HEEC(P<0.05)。与Control组相比,si-circ-0058063组细胞中circ-0058063表达水平、细胞存活率、克隆细胞数、GSH水平、p-ERK1/2/ERK1/2和p-p38MAPK/p38MAPK比值及SLC7A11、GPX4蛋白表达水平均明显降低(P<0.05),细胞中Fe^(2+)、MDA及ROS水平均明显增加(P<0.05);与si-circ-0058063组相比,si-circ-0058063+ISO组细胞中circ-0058063表达水平、细胞存活率、克隆细胞数、GSH水平、p-ERK1/2/ERK1/2和p-p38MAPK/p38MAPK比值及SLC7A11、GPX4蛋白表达水平均明显升高(P<0.05),Fe^(2+)、MDA及ROS水平均明显降低(P<0.05)。结论敲减circ-0058063可抑制食管癌细胞增殖,诱导食管癌细胞铁死亡,其作用机制可能与抑制ERK/MAPK信号通路激活有关。Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe^(2+),malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe^(2+),MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe^(2+),MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.

关 键 词：circ-0058063 食管癌 铁死亡 ERK/MAPK信号通路 

分 类 号：R735.1[医药卫生—肿瘤]