摘要
线粒体是持续进行分裂和融合的动态细胞器。近年来,除了线粒体代谢作用相关的研究之外,线粒体动力学也开始逐渐引起研究的关注。越来越多的研究表明,线粒体动力学与肿瘤细胞生物学行为具有相关性。线粒体分裂蛋白1(mitochondrial fission protein 1,FIS1)介导线粒体分裂复合物的组装,参与线粒体分裂,是线粒体融合分裂过程中重要的蛋白质。然而,鲜有研究揭示FIS1在人宫颈癌中的表达及其作用。本研究对比了宫颈癌组织以及癌旁组织的转录物组数据,结果显示,与癌旁组织相比,人宫颈癌组织中的FIS1 mRNA水平明显降低(P<0.01)。进一步进行宫颈癌组织FIS1高表达组与低表达组的差异基因分析,发现差异基因主要与线粒体功能相关。随后,进行FIS1过表达后HeLa细胞增殖、迁移、线粒体裂变以及ROS水平的相关分析。结果显示,过表达FIS1基因,HeLa细胞增殖及迁移能力显著降低,细胞内线粒体裂变程度加剧并且细胞内ROS水平升高。综合以上结果,FIS1在人宫颈癌细胞中表达水平较低,而过表达FIS1可促使宫颈癌细胞因线粒体动力学失衡而发生一系列生物学功能异常。因此,本研究为进一步研究FIS1在宫颈癌治疗中的作用奠定了重要基础。
Mitochondria are dynamic organelles that continuously divide and fuse.In recent years,in addition to the studies related to mitochondrial metabolism,the unique dynamics of mitochondria have gradually attracted researchers’attention.A growing body of research has revealed that mitochondrial dynamics are related to the biological behavior of tumor cells.Mitochondrial fission proteins(mitochondrial fission protein 1,FIS1)mediate the assembly of mitochondrial fission complexes and participate in the execution of mitochondrial fission.They are important proteins in the process of mitochondrial fusion and fission.However,few studies have revealed the expression and role of FIS1 in human cervical cancer.In this study,the expression level of FIS1 in human cervical cancer tissues and paracancer tissues were compared.The results showed that the level of FIS1 mRNA in human cervical cancer tissues was significantly lower than that in paracancer tissues(P<0.01).Further KEGG pathway and GO Term-BP pathway analysis showed that the differential genes are mainly related to mitochondrial biological functions.Subsequently,HeLa cells with overexpressed FIS1 were investigated for their proliferation,migration,mitochondrial fission and ROS levels.The experimental results showed that FIS1 overexpression decreased HeLa cell proliferation and migration ability,enhanced mitochondrial fission and higher ROS levels.In conclusion,the expression of FIS1 in human cervical cancer cells was attenuated,while overexpression of FIS1 resulted in a series of abnormal biological functions in human cervical cancer cells.Further studies can be carried out to investigate the role of FIS1 in the treatment of human cervical cancer.
作者
丛瑞
李星宇
霍楠
朱祥
薛春源
房廖鑫
亢小峰
朱俊闻
杜祎萌
徐小洁
CONG Rui;LI Xing-Yu;HUO Nan;ZHU Xiang;XUE Chun-Yuan;FANG Liao-Xin;KANG Xiao-Feng;ZHU Jun-Wen;DU Yi-Meng;XU Xiao-Jie(Department of Cellular Engineering,Beijing Institute of Biotechnology,Beijing 100850,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2022年第7期926-935,共10页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学优秀青年基金项目(No.81822037)
国家自然科学基金面上项目(No.81972446)
北京市自然科学基金项目(No.JQ19028)资助。
关键词
线粒体分裂蛋白1
癌症基因组数据集
线粒体
宫颈癌
生物信息学
mitochondrial fission protein 1(FIS1)
The Cancer Genome Atlas(TCGA)
mitochondria
cervical cancer
bioinformatics
