人转录因子FoxM1B的生物信息学分析
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摘要
目的:分析预测人转录因子FoxM1B启动子及蛋白结构和功能。方法:运用生物信息学软件对人FoxM1B基因的启动子区域及其蛋白的理化性质、跨膜区、信号肽和亲疏水性进行预测分析;利用软件模拟生成人FoxM1B蛋白质的三级结构图像,了解与其相互作用的蛋白网络。结果:采用生物信息学软件预测出人FoxM1B基因5'侧翼存在转录起始位点及启动子,且启动子(1300～1900 bp)的侧翼有1个CpG岛。人FoxM1B蛋白是亲水性蛋白,且不包含跨膜结构域和信号肽;在二级结构中,无规卷曲是其主要折叠方式,模拟生成蛋白质三级结构图像与二级结构预测一致。人FoxM1B蛋白与CCNB1、CCNA2、MYBL2、CDK1和PLK1等蛋白存在相互作用,可能通过这些蛋白参与细胞周期和DNA损伤修复过程。结论:对人FoxM1B基因及其编码蛋白的性质、结构和互作蛋白等进行了预测分析,为后续实验研究提供了依据和线索,奠定了重要的信息基础。
Objective: To analyze and predict the structure and function of human transcription factor FoxM1 gene and protein. Methods: Bioinformatics softwares were applied to analyze and predict the physical and chemical properties, transmembrane regions, signal peptides and hydrophilicity of FoxM1 B promoter and protein. The tertiary structure of human FoxM1 B protein was simulated by software, and an interaction net between FoxM1 B and other proteins was obtained. Results: The transcription start site and promoters were found in the 5' unconding region of human FoxM1 B gene by online bioinformatics tools. Besides, one CpG island was found on the flank of promoter(1300～1900 bp). It was found that FoxM1 B was an hydrophilic protein without signal peptide and properties, structure and function of human FoxM1 B are predicted and transmembrane domain by analyzing the protein FoxM1 B. In the secondary structure, random coiling is the main folding mode of human FoxM1 B protein. The 3 D structure of FoxM1 B protein was generated as expected by secondary structure. It was finally found that the human FoxM1 B protein might interact with CCNB1, CCNA2, MYBL2, CDK1, and PLK1. In addition, FoxM1 B was considered to involve into the cell cycle and DNA damage repair process through these proteins. Conclusion: The properties, structure and function of human FoxM1 B are predicted and analyzed, which provide basis and clues for subsequent experimental research and lay an important information foundation.
Objective: To analyze and predict the structure and function of human transcription factor FoxM1 gene and protein. Methods: Bioinformatics softwares were applied to analyze and predict the physical and chemical properties, transmembrane regions, signal peptides and hydrophilicity of FoxM1 B promoter and protein. The tertiary structure of human FoxM1 B protein was simulated by software, and an interaction net between FoxM1 B and other proteins was obtained. Results: The transcription start site and promoters were found in the 5' unconding region of human FoxM1 B gene by online bioinformatics tools. Besides, one CpG island was found on the flank of promoter(1300～1900 bp). It was found that FoxM1 B was an hydrophilic protein without signal peptide and properties, structure and function of human FoxM1 B are predicted and transmembrane domain by analyzing the protein FoxM1 B. In the secondary structure, random coiling is the main folding mode of human FoxM1 B protein. The 3 D structure of FoxM1 B protein was generated as expected by secondary structure. It was finally found that the human FoxM1 B protein might interact with CCNB1, CCNA2, MYBL2, CDK1, and PLK1. In addition, FoxM1 B was considered to involve into the cell cycle and DNA damage repair process through these proteins. Conclusion: The properties, structure and function of human FoxM1 B are predicted and analyzed, which provide basis and clues for subsequent experimental research and lay an important information foundation.
引文
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[15]Yang H,Wen L,Wen M,et al.FoxM1B promotes epithelial-mesenchymal transition,invasion,and migration of tongue squamous cell carcinoma cells through a cMet/AKT-dependent positive feedback loop[J].AntiCancer Drugs,2018,29(3):216-226.
[16]朱霞,鲁康洋,江燕,等.FoxM1B抑制剂下调Rad51增敏顺铂对骨肉瘤耐药细胞的化疗抑制作用[J].临床与实验病理学杂志,2017,(4):53-57.
[2]刘宁,刘雪娇,潘昕.Fox基因家族在胶质瘤中的研究进展[J].徐州医学院学报,2016,36(5):343-346.
[3]杨竹.Fox基因家族与卵巢疾病的研究进展[J].重庆医科大学学报,2007,32(4):440-441.
[4]丁政,樊友本.FOX家族基因在肿瘤形成中的作用研究进展[J].国际外科学杂志,2013,40(10):684-688.
[5]Ye H,Kelly T F,Samadani U,et al.Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues[J].Mol Cell Biol,1997,17(3):1626-1641.
[6]Chen X,Muller G A,Quaas M,et al.The Forkhead transcription factor FOXM1B controls cell cycle-dependent gene expression through an atypical chromatin binding mechanism[J].Mol Cell Biol,2013,33(2):227-236.
[7]Cao S,Lin L,Xia X,et al.MicroRNA-761 promotes the sensitivity of colorectal cancer cells to 5-Fluorouracil through targeting FOXM1B[J].Oncotarget,2018,9(1):321-331.
[8]张明杰,范承哲,李少一,等.FoxM1B在胶质瘤对卡氮芥化疗抵抗中的作用[J].现代肿瘤医学,2015,23(8):1044-1047.
[9]张立洁.FOXM1B在人肝癌中的表达及临床意义及其与MTA1和MMP-2的关系[D].南宁:广西医科大学,2010.
[10]Kalinichenko V V,Major M L,Wang X,et al.Fox M1Btranscription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor.[J].Genes Dev,2004,18(7):830-850.
[11]万婕,祝琳,雷越,等.FoxM1B通过Wnt/β-catenin信号通路对鼻咽癌细胞5-8F增殖、迁移的影响[J].第三军医大学学报,2018,(5):380-386.
[12]唐双意,焦杨,黎乐群.基因FoxM1B在细胞增殖和肿瘤发生中的意义[J].癌症,2008,27(8):894-896.
[13]谭拥军,陈含笑.转录因子FOXM1剪接异构体在乳腺癌EMT过程中的初步研究[J].湖南大学学报(自然科学版),2015,42(12):100-106.
[14]Kong F F,Zhu Y L,Yuan H H,et al.FOXM1 regulated by ERK pathway mediates TGF-β1-induced EMT in NSCLC[J].Oncol Res,2014,22(1):29-37.
[15]Yang H,Wen L,Wen M,et al.FoxM1B promotes epithelial-mesenchymal transition,invasion,and migration of tongue squamous cell carcinoma cells through a cMet/AKT-dependent positive feedback loop[J].AntiCancer Drugs,2018,29(3):216-226.
[16]朱霞,鲁康洋,江燕,等.FoxM1B抑制剂下调Rad51增敏顺铂对骨肉瘤耐药细胞的化疗抑制作用[J].临床与实验病理学杂志,2017,(4):53-57.