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基于生物信息学揭示ceRNA调控网络在结直肠癌中的作用
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作者 刘琳 费素娟 苗蓓 《激光生物学报》 CAS 2024年第4期365-376,共12页
为探索结直肠癌(CRC)相关的竞争性内源RNA(ceRNA)网络调控机制,寻找治疗CRC的潜在靶点,本研究从基因表达综合(GEO)数据库中下载CRC相关环状RNA(circRNA)数据集,应用稳健排序整合(RRA)算法、加权基因共表达网络分析(WGCNA)筛选差异表达ci... 为探索结直肠癌(CRC)相关的竞争性内源RNA(ceRNA)网络调控机制,寻找治疗CRC的潜在靶点,本研究从基因表达综合(GEO)数据库中下载CRC相关环状RNA(circRNA)数据集,应用稳健排序整合(RRA)算法、加权基因共表达网络分析(WGCNA)筛选差异表达circRNA,采用实时荧光定量PCR(RT-qPCR)验证了筛选的circRNA(hsa_circRNA_057090、hsa_circRNA_092566)呈环状,且在CRC组织、CRC细胞系中均高表达。在circBank及CircInteractome数据库中预测与circRNA相结合的微RNA(miRNA),在TargetScan、miRDB数据库中预测miRNA的靶基因,从癌症基因组图谱(TCGA)数据库中筛选CRC差异表达mRNA,两者取交集后得到差异表达靶基因,构建出ceRNA调控网络。应用DAVID软件、String数据库、Cytoscape软件及基因表达谱互动分析(GEPIA)数据库对靶基因进行基因本体(GO)富集分析、京都基因和基因百科全书(KEGG)富集分析、蛋白质-蛋白质相互作用网络(PPI)构建及生存分析。从PPI网络中筛选出10个核心基因,最终构建出circRNA-miRNA-核心基因网络。GO富集分析和KEGG富集分析显示,核心基因主要参与化学突触传递、配体门控离子通道活性等过程,且在cAMP等多个信号通路中显著富集。生存分析显示,2个核心基因SNAP25、ATP2B2的表达水平与CRC患者预后显著相关。本研究鉴定的hsa_circRNA_057090、hsa_circRNA_092566及构建的ceRNA调控网络可能为CRC提供新的生物标志物或潜在的治疗靶点。 展开更多
关键词 结直肠癌 环状RNA 竞争性内源RNA 核心基因网络 治疗靶点
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Topological origin of global attractors in gene regulatory networks
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作者 ZHANG YunJun OUYANG Qi GENG Zhi 《Science China(Physics,Mechanics & Astronomy)》 SCIE EI CAS CSCD 2015年第2期101-108,共8页
Fixed-point attractors with global stability manifest themselves in a number of gene regulatory networks. This property indicates the stability of regulatory networks against small state perturbations and is closely r... Fixed-point attractors with global stability manifest themselves in a number of gene regulatory networks. This property indicates the stability of regulatory networks against small state perturbations and is closely related to other complex dynamics. In this paper, we aim to reveal the core modules in regulatory networks that determine their global attractors and the relationship between these core modules and other motifs. This work has been done via three steps. Firstly, inspired by the signal transmission in the regulation process, we extract the model of chain-like network from regulation networks. We propose a module of "ideal transmission chain(ITC)", which is proved sufficient and necessary(under certain condition) to form a global fixed-point in the context of chain-like network. Secondly, by examining two well-studied regulatory networks(i.e., the cell-cycle regulatory networks of Budding yeast and Fission yeast), we identify the ideal modules in true regulation networks and demonstrate that the modules have a superior contribution to network stability(quantified by the relative size of the biggest attraction basin). Thirdly, in these two regulation networks, we find that the double negative feedback loops, which are the key motifs of forming bistability in regulation, are connected to these core modules with high network stability. These results have shed new light on the connection between the topological feature and the dynamic property of regulatory networks. 展开更多
关键词 Boolean model BISTABILITY network module ROBUSTNESS
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