摘要
目的:探讨白介素增强子结合因子2(interleukin enhancer binding factor 2,ILF2)在非小细胞肺癌细胞增殖中的作用并探讨其机制。方法:选取来自某医院2016年3月至2022年6月间非小细胞肺癌患者癌及癌旁组织各15例,采用shRNA方法抑制非小细胞肺癌A549和H1299细胞系中ILF2表达,通过qRT-PCR、免疫组化和Western blot方法检测组织和细胞中ILF2的mRNA和蛋白表达,采用克隆形成和BrdU方法分析A549和H1299细胞体外增殖,无胸腺小鼠经皮下注射A549细胞后通过免疫组化技术观察Ki67和活化caspase 3(cleaved caspase 3)的表达,通过分析A549和H1299细胞中线粒体DNA(mtDNA)、线粒体质量和线粒体膜电位观察线粒内稳态。结果:与癌旁组相比,肺癌组织中ILF2的mRNA和蛋白表达均显著上调(P均<0.05);抑制ILF2表达可降低A549和H1299细胞体外克隆形成和增殖能力以及A549细胞在小鼠体内肺癌细胞生长能力(P均<0.05),小鼠肺组织中Ki67表达显著降低(P<0.05),A549和H1299细胞中mtDNA和线粒体质量均显著降低,线粒体膜电位显著上调(P均<0.05);过表达ILF2可促进A549和H1299细胞中体外克隆形成和增殖能力以及mtDNA和线粒体质量,降低线粒体膜电位(P均<0.05)。结论:ILF2在非小细胞肺癌进展过程中发挥重要作用,可能与破坏线粒体内稳态有关。
Objective:To investigate the role of interleukin enhancer binding factor 2(ILF2)in the proliferation of non-small cell lung cancer cells and to explore its mechanism.Methods:Lung cancer and adjacent normal tissue samples were obtained from non-small cell lung cancer patients(n=15)in a hospital from March 2016 to June 2022.The expression of ILF2 in A549 and H1299 cell lines of non-small cell lung cancer was inhibited by shRNA assay.The expression of ILF2 mRNA and protein in tissues and cells was detected by qRT-PCR,immunohistochemistry and Western blot assay.The proliferation of A549 and H1299 cells in vitro was analyzed by clone formation and BrdU assay,and the expression of Ki67 and cleaved caspase 3 was observed by immunohistochemistry after subcutaneously injection of lung cancer cells A549 in athymic nude mice.The mitochondrial homeostasis was observed by mtDNA,mitochondrial mass and mitochondrial membrane potential in A549 and H1299 cells.Results:Compared with the adjacent group,the expression of ILF2 mRNA and protein in lung cancer tissues was significantly upregulated(all P<0.05).There was a suppression of clonal formation and proliferation in A549 and H1299 cells in vitro and in vivo by inhibiting ILF2 expression(P<0.05).The expression of Ki67 in mice lung tissues was significantly reduced(P<0.05),and the levels of mtDNA and mitochondrial mass were significantly reduced,and the mitochondrial membrane potential was significantly increased in A549 and H1299 cells(all P<0.05).There was a increased capability of clonal formation and proliferation and mtDNA and mitochondrial mass,an decreased level of mitochondrial membrane potential in A549 and H1299 cells after ILF2 overexpressed(all P<0.05).Conclusion:ILF2 plays an important role in non-small cell lung cancer progression,which may be related to the destruction of mitochondrial homeostasis.
作者
贺丽华
赵猛
刘树业
朱彧
HE Lihua;ZHAO Meng;LIU Shuye;ZHU Yu(The Third Central Clinical College of Tianjin Medical University,Tianjin 300170,China;Department of Clinical Laboratory,the Third Central Hospital of Tianjin,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases,Artificial Cell Engineering Technology Research Center of Tianjin,Tianjin Institute of Hepatobiliary Disease,Tianjin 300170,China;Department of Clinical Laboratory,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,China)
出处
《现代肿瘤医学》
CAS
2024年第8期1387-1392,共6页
Journal of Modern Oncology
基金
国家自然科学基金资助项目(编号:81602026)
天津市临床重点学科(专科)建设项目(编号:TJYXZDXK-047A)。
关键词
白介素增强子结合因子2
非小细胞肺癌
线粒体内稳态
interleukin enhancer binding factor 2
non-small cell lung cancer
mitochondrial homeostasis
