长链非编码RNA LINC00313通过铁死亡抵抗促进肺癌细胞的增殖和迁移  

Long non-coding RNA LINC00313 promotes proliferation and migration of lung cancer cells through ferroptosis resistance

作　　者：黄琳[1] 李彬[1] 胡作为[1] HUANG Lin;LI Bin;HU Zuowei(Wuhan No.1 Hospital,Hubei Wuhan 430022,China)

机构地区：[1]武汉市第一医院,湖北武汉430022

出　　处：《现代肿瘤医学》2023年第9期1614-1618,共5页Journal of Modern Oncology

基　　金：湖北省武汉市卫生健康委员会医学科研青年项目(编号:WZ20Q04)。

摘　　要：目的:探讨长链非编码RNA(LncRNA)LINC00313促进肺癌细胞增殖、迁移的作用机制。方法:选用肺癌细胞株A549、H466、H1299、H522,通过实时荧光定量PCR检测LncRNA LINC00313在肺癌细胞中的表达。采用Transwell实验和划痕实验等表型实验检测肺癌细胞侵袭和迁移情况。敲除LINC00313,CCK-8实验及流式细胞仪检测过量GPX4对肺癌细胞增殖和细胞凋亡的影响。LINC00313基因敲除后,检测在Erastin或RSL-3处理的A549细胞内的铁水平及ROS含量,探讨LINC00313与肺癌细胞铁死亡的关系。结果:与正常细胞相比,肺癌细胞中LINC00313的表达明显升高(P<0.05);表型实验结果显示LINC00313促进肺癌细胞增殖,同时抑制其凋亡。Transwell实验和划痕实验结果表明LINC00313可以促进肺癌细胞侵袭和迁移。GPX4过表达可以逆转LINC00313敲除导致肺癌细胞的增殖下降和凋亡增加。在Erastin或RSL3处理的A549细胞中,LINC00313基因敲除后细胞内的铁和Fe^(2+)水平下降,脂质过氧化ROS(Lipid ROS)含量产生显著减少。结论:肺癌细胞中LINC00313表达明显升高,过表达LINC00313可以促进肺癌细胞侵袭和迁移,作用机制可能与促进肺癌细胞铁死亡抵抗,从而导致肺癌的发生及转移有关。Objective:To investigate the mechanism of long non-coding RNA(LncRNA)LINC00313 in promoting the proliferation and metastasis of lung cancer cells.Methods:Lung cancer cell lines A549,H466,H1299 and H522 were selected,and the expression of LINC00313 in lung cancer cells was detected by real-time PCR.Transwell test and scratch test were used to detect the invasion and migration of lung cancer cells.The effect of excess GPX4 on proliferation and apoptosis of lung cancer cells was detected by CCK-8 assay and flow cytometry after knockout of LINC00313.To investigate the relationship between LINC00313 and ferroptosis in lung cancer cells by detecting iron levels and ROS content in Erastin or RSL3 treated A549 cells after LINC00313 gene knockout.Results:Compared with normal cells,the expression of LINC00313 in lung cancer cells was significantly increased(P<0.05).Phenotypic experiments showed that LINC00313 promoted the proliferation of lung cancer and inhibited its apoptosis.The results of Transwell assay and scratch assay showed that LINC00313 could promote the invasion and migration of lung cancer cells.GPX4 overexpression reversed the decreased proliferation and increased apoptosis induced by LINC00313 knockdown.In Erastin or RSL-3 treated A549 cells,the levels of iron and Fe^(2+) in the cells decreased after LINC00313 knockdown,and the production of lipid ROS decreased significantly.Conclusion:The expression of LINC00313 is significantly increased in lung cancer cells.Overexpression of LINC00313 can promote the invasion and migration of lung cancer cells,and the mechanism may be related to the promotion of ferroptosis resistance in lung cancer cells,thus leading to the occurrence and metastasis of lung cancer.

关 键 词：肺癌 LncRNA LINC00313 铁死亡 

分 类 号：R734.2[医药卫生—肿瘤]