miR-203a-3p通过ALOX15途径抑制胃癌细胞铁死亡  

miR-203a-3p inhibits iron death in gastric cancer cells via the ALOX15 pathway

作　　者：唐凤英[1] 董汾 曾玉婷 高二鹏 张锋利[1] 闫娣 TANG Fengying;DONG Fen;ZENG Yuting;GAO Erpeng;ZHANG Fengli;YAN Di(Department of Gastroenterology,the Second Affiliated Hospital,Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China)

机构地区：[1]陕西中医药大学第二附属医院消化内科,陕西省咸阳市712000

出　　处：《中南医学科学杂志》2022年第6期796-800,共5页Medical Science Journal of Central South China

基　　金：陕西省科技计划项目(2020XKTD-A01)。

摘　　要：目的探讨miR-203a-3p通过ALOX15途径调控胃癌细胞铁死亡的机制。方法检测胃癌组织和癌旁正常组织的铁死亡指标——活性氧诱导脂质过氧化(lipid-ROS)水平。对胃癌组织miR-203a-3p与lipid-ROS进行Pearson相关性分析。在胃正常细胞和胃癌细胞株中过表达或敲低相关分子后,检测其lipid-ROS和线粒体膜电位(MMP)。结果miR-203a-3p水平胃癌组织高于癌旁正常组织,胃癌细胞株高于胃正常细胞;lipid-ROS水平胃癌组织低于癌旁正常组织,胃癌细胞株低于胃正常细胞(P<0.05)。在胃癌组织中,miR-203a-3p与lipid-ROS呈负相关(P<0.05)。胃癌组织ALOX15 mRNA低于癌旁正常组织(P<0.05)。过表达miR-203a-3p后,胃正常细胞lipid-ROS、胃癌细胞MMP、所有细胞ALOX15 mRNA和蛋白水平降低;敲低miR-203a-3p后,胃癌细胞lipid-ROS、所有细胞ALOX15 mRNA和蛋白升高;敲低ALOX15时胃正常细胞lipid-ROS和胃癌细胞MMP降低,过表达ALOX15后胃癌细胞lipid-ROS升高(P<0.05)。结论胃癌细胞高表达的miR-203a-3p可靶向ALOX15,减少ALOX15表达,抑制其铁死亡发生。Aim To investigate the mechanism by which miR-203a-3p regulates iron death in gastric cancer cells through the ALOX15 pathway.Methods The levels of iron death indicators(reactive oxygen species-induced lipid peroxidation(lipid-ROS))were detected in gastric cancer tissues and normal tissues adjacent to the cancer.Pearson correlation analysis was performed between miR-203a-3p and lipid-ROS in gastric cancer tissues.The lipid-ROS and mitochondrial membrane potential(MMP)were examined after overexpression or knockdown of the related molecules in gastric normal cells and gastric cancer cell lines.Results The level of miR-203a-3p in gastric cancer tissues was higher than that in normal adjacent tissues,and the level of miR-203a-3p in gastric cancer cell lines was higher than that in normal gastric cells;Lipid ROS level in gastric cancer tissues was lower than that in normal adjacent tissues,and gastric cancer cell lines were lower than that in normal gastric cells(P<0.05).In gastric cancer tissues,miR-203a-3p was negatively correlated with lipid-ROS(P<0.05).ALOX15 mRNA in gastric cancer was lower than that in normal adjacent tissues(P<0.05).After overexpression of miR-203a-3p,the level of lipid-ROS in normal gastric cells,MMP in gastric cancer cells,and ALOX15 mRNA and protein in all cells decreased;knock down miR-203a-3p,the lipid-ROS of gastric cancer cells,ALOX15 mRNA and protein of all cells increased;lipid-ROS in normal gastric cells and MMP in gastric cancer cells were decreased when ALOX15 was knocked down,while lipid-ROS in gastric cancer cells was increased after overexpression of ALOX15(P<0.05).Conclusion High expression of miR-203a-3p in gastric cancer cells targets ALOX15,reduces ALOX15 expression and inhibits iron death occurrence.

关 键 词：miR-203a-3p ALOX15 胃癌细胞 铁死亡 

分 类 号：R735.2[医药卫生—肿瘤]