ceRNA介导的多层次调控网络功能研究及其在线分析平台构建

Recent studies have shown that ceRNA activity orchestrated large-scale transcriptional regulatory networks and greatly expanded the functional genetic information of diverse organisms, it suggest that existence of the novel RNA-miRNA pathway except the traditional miRNA-RNA one, the RNA-miRNA mode play important roles in diverse life activities such as cell growth and differentiation, embryonic development and tumorigenesis. but the specific mechanism of this mode is poorly understood, in addition, ceRNAs are intertwined with other regulatory factors and form complex, multi-level regulatory networks in cell microenvironment, which increase the difficulty of its functional studies, the emergence of high-throughput sequencing technology provide the rules which can measure different aspects of ceRNA regulatory functions and provides multi-level data to support the study of ceRNA-mediated regulatory networks, In this project we will construct the ceRNA-mediated hierarchical network based on gene expression data, ChIP-seq data to reveal the ceRNA regulatory function in various biological processes such as cell proliferation, differentiation and its influence and control mechanism of human disease from different levels, we also build a series rules to quantify these regulatory mechanisms and draw ceRNA-mediated multi-level regulatory map. We hope this will help the biologist to understand the specific molecular and biological mechanisms of the ceRNA-mediated regulation and open new perspectives for ceRNA functional research.

近期的研究发现ceRNA活性形成的大规模转录调控网络大大扩展了人类基因组中的功能型遗传信息，揭示了除传统的miRNA-RNA作用方式外，还存在反向的RNA-miRNA作用方式，这种作用方式在生物体各项生命活动如细胞生长和分化、胚胎发育以及肿瘤的发生和发展中发挥着重要作用，但目前对这种作用方式的具体机制知之甚少，此外在细胞微环境中的ceRNA和其他调控因子又有着密切的交互作用，他们在细胞微环境中形成了复杂的多层次调控网络，这更增加其功能研究的困难性，而高通量测序技术出现从不同侧面度量了这些调控功能的效应，为我们研究ceRNA及其介导的多层次调控网络提供了数据支持，本研究拟基于基因表达数据，ChIP-seq数据构建ceRNA介导的多层次调控模型从不同调控层次上揭示ceRNA网络对细胞增殖、分化及人类疾病等各种生命活动过程中的调控，并量化这些调控机制，绘制多层次的ceRNA调控功能图谱。

ceRNA介导的调控网络大大扩展了人类基因组中的功能型遗传信息，揭示了除传统的miRNA-RNA作用方式外，还存在通过miRNA调节的RNA-RNA作用方式，这种作用方式在生物体各项生命活动如细胞生长和分化、胚胎发育、肿瘤的发生和发展及肌肉老龄化中发挥着重要作用，但目前对这种作用方式的具体机制知之甚少，此外在细胞微环境中的ceRNA和其他调控因子又有着密切的交互作用，他们在细胞微环境中形成了复杂的多层次调控网络，这更增加其功能研究的困难性，而高通量测序技术出现从不同侧面度量了这些调控功能的效应，为我们研究ceRNA及其介导的多层次调控网络提供了数据支持，本研究基于基因表达数据，ChIP-seq数据构ceRNA介导的多层次调控模型从不同调控层次上揭示ceRNA网络对细胞增殖、分化、人类疾病及肌肉老龄化等各种生命活动过程中的调控，并量化这些调控机制，绘制了多层次的ceRNA调控功能图谱。本研究基于多维高通量数据构建的ceRNA调控网络分析平台及分析算法已应用到肌肉老龄化及机械性功能丧失过程中关键ceRNA及其介导的调控网络，并经过实验证实了预测结果的可靠性为肌肉老龄化后续的研究提供了新的分子靶点和干预策略。