基于单细胞RNA-seq数据识别介导癌症hallmark活性的关键lncRNA及其功能研究

批准号:
32000459
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
徐锦远
依托单位:
学科分类:
生物大数据解析
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
徐锦远
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中文摘要
癌症的发病和进展过程中存在着复杂的异质性状态,为解读肿瘤内癌症hallmark的异常机制带来巨大挑战。单细胞RNA-seq技术的出现为精细刻画肿瘤内转录状态、挖掘影响癌症hallmark的潜在因素创造了条件,而lncRNA凭借其表达的高度特异性以及广泛的调控作用,有望成为解读癌症hallmark活性机制的突破口。本项目拟整合癌症单细胞RNA-seq数据,系统刻画单细胞水平癌症hallmark的活性状态,推断lncRNA介导的调控网络,通过整合分析单细胞水平lncRNA的调控能力、lncRNA的表达及其下游基因与癌症hallmark活性的关联,识别介导各个癌症hallmark活性的关键lncRNA及其调控机制,并进行体内外实验验证。同时,开发癌症hallmark的单细胞综合分析平台,为研究肿瘤进展机制提供新手段,为癌症的诊断和治疗以及靶向药物的研发提供新策略。
英文摘要
During the development and progression of cancer, complex heterogeneous states occurred, which poses great challenges for the interpretation of the abnormal mechanisms of the hallmarks of cancer in tumors. The emergence of single-cell RNA-seq technology has created conditions for finely characterizing the transcription status in tumors and exploring the potential factors affecting the hallmarks of cancer. Considering their highly specific expression patterns and extensive regulatory effects, lncRNAs are expected to be key roles to accurately interpret the activity of the hallmarks of cancer. In this study, we integrate single-cell RNA-seq data to systematically characterize the activity state of the hallmarks of cancer at the single-cell level and infer lncRNA-mediated regulatory networks. Through integration analysis of the regulation ability of lncRNA, the expression of lncRNA and its downstream genes and their associations with the activity of the hallmarks of cancer at the single-cell level, we identify the key lncRNAs that mediated the activity of each hallmark of cancer and their regulatory mechanisms. We use in vitro and in vivo experiments to validate the biological functions of the key lncRNAs. Besides, we develop an integrative bioinformatics platform for analyzing the hallmarks of cancer at the single-cell level. The implementation of this work will provide valuable tools for studying the mechanisms of tumor progression and provide new strategies to the diagnosis and treatment of cancer and the development of targeted drugs.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1016/j.ygeno.2022.110412
发表时间:2022-06-29
期刊:GENOMICS
影响因子:4.4
作者:Cheng,Peng;Lan,Yujia;Xu,Jinyuan
通讯作者:Xu,Jinyuan
DOI:10.1002/1878-0261.13499
发表时间:2023-11
期刊:Molecular oncology
影响因子:6.6
作者:Xu J;Pang B;Lan Y;Dou R;Wang S;Kang S;Zhang W;Liu Y;Zhang Y;Ping Y
通讯作者:Ping Y
DOI:10.1007/s12094-022-02977-7
发表时间:2022-11-01
期刊:CLINICAL & TRANSLATIONAL ONCOLOGY
影响因子:3.4
作者:Wang,Zihang;Zhang,Lan;Song,Wuqi
通讯作者:Song,Wuqi
DOI:10.1093/stmcls/sxac088
发表时间:2023
期刊:Stem Cells
影响因子:--
作者:Haoteng Yan;Jiali Zhu;Yanyan Ping;Min Yan;Gaoming Liao;Huating Yuan;Yao Zhou;Fengyu Xiang;Bo Pang;Jinyuan Xu;Lin Pang
通讯作者:Lin Pang
国内基金
海外基金
