miR-627-3p并发靶向STK11/KEAP1调控肺腺癌的铁死亡研究  

miR-627-3p Concurrently Targeting STK11/KEAP1 Regulates Ferroptosis in Lung Adenocarcinoma

作　　者：张苗苗 田君娜[1] 孙颖颖 ZHANG Miaomiao;TIAN Junna;SUN Yingying(Nanyang Central Hospital,Nanyang,473000)

机构地区：[1]河南省南阳市中心医院,473000

出　　处：《实用癌症杂志》2023年第7期1066-1070,共5页The Practical Journal of Cancer

摘　　要：目的探讨miR-627-3p调控肺腺癌铁死亡的潜在机制。方法纳入肺腺癌患者126例,收集肺腺癌组织和癌旁组织后使用miRNA微阵列检测差异miRNA并分析miRNA与肺腺癌患者生存率的相关性。过表达或敲低miRNA后检测肺腺癌细胞Calu-3的增殖水平和铁死亡水平。使用miRDB数据库分析miR-627-3p发挥生物学功能的潜在底物,选取评分最高的60个基因进行siRNA敲低筛选以鉴定miR-627-3p的底物。结果miRNA微阵列分析发现有27种miRNA变化显著,其中14种miRNA在肺腺癌组织中表达下调,13种miRNA在肺腺癌组织中表达上调。其中,miR-627-3p高表达的肺腺癌患者生存率优于miR-627-3p低表达的肺腺癌患者。过表达miR-627-3p后,肺腺癌细胞Calu-3的细胞增殖水平下降(P<0.05),铁死亡水平上升(P<0.05);敲低miR-627-3p后,肺腺癌细胞Calu-3的细胞增殖水平上升(P<0.05),铁死亡水平下降(P<0.05)。敲低STK11或KEAP1时肺腺癌细胞Calu-3的细胞增殖水平下降(P<0.05)、铁死亡水平上升(P<0.05);过表达STK11或KEAP1时肺腺癌细胞Calu-3的细胞增殖水平上升(P<0.05)、铁死亡水平下降(P<0.05)。过表达miR-627-3p后,肺腺癌细胞Calu-3中STK11或KEAP1的mRNA和蛋白水平下降;敲低miR-627-3p后,肺腺癌细胞Calu-3中STK11或KEAP1的mRNA和蛋白水平上升。此外,miR-627-3p结合STK11或KEAP1的3'端非翻译区。结论miR-627-3p通过并发靶向STK11/KEAP1促进肺腺癌的铁死亡水平。miR-627-3p可能是治疗肺腺癌的有用治疗靶点。Objective To explore the potential mechanism of miR-627-3p regulating ferroptosis in lung adenocarcinoma.Methods A total of 126 patients with lung adenocarcinoma were included.After collecting lung adenocarcinoma tissue and adjacent tissue,miRNA microarray was used to detect differential miRNAs and analyze the relationship between miRNA and the survival rate of lung adenocarcinoma patients.The proliferation level and ferroptosis of lung adenocarcinoma cells were detected after overexpression or knockdown of miRNA.The potential substrates of miR-627-3p to exert biological functions were analyzed using the miRDB database,and the 60 genes with the highest scores were selected for siRNA knockdown screening to identify the substrates of miR-627-3p.Results miRNA microarray analysis revealed significant changes in 27 mirnas,among which 14 mirnas were down-regulated and 13 mirnas were up-regulated in lung adenocarcinoma tissues.Among them,the survival rate of lung adenocarcinoma patients with high miR-627-3p expression was better than that of lung adenocarcinoma patients with low miR-627-3p expression.After overexpression of miR-627-3p,the cell proliferation level of lung adenocarcinoma cell Calu-3 was decreased(P<0.05),while the iron death level was increased(P<0.05).After knockdown of miR-627-3p,the cell proliferation level of lung adenocarcinoma cell Calu-3 increased(P<0.05),while the iron death level decreased(P<0.05).When STK11 or KEAP1 was knocked down,the cell proliferation level of lung adenocarcinoma cell Calu-3 decreased(P<0.05),and the iron death level increased(P<0.05).Overexpression of STK11 or KEAP1 increased the cell proliferation level of Calu-3 in lung adenocarcinoma cells(P<0.05)and decreased the iron death level(P<0.05).After overexpression of miR-627-3p,the mRNA and protein levels of STK11 or KEAP1 in lung adenocarcinoma cells Calu-3 decreased.After knockdown of miR-627-3p,mRNA and protein levels of STK11 or KEAP1 in lung adenocarcinoma cells Calu-3 increased.In addition,miR-627-3p binds to the 3'-ter

关 键 词：miR-627-3p STK11 KEAP1 肺腺癌 铁死亡 

分 类 号：R734.2[医药卫生—肿瘤]