功能代谢组学在胶质瘤研究中的应用
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- 英文论文题名：The application of functional metabolomics in the study of glioma
- 论文作者：许国旺 ; 高鹏 ; 刘杨 ; 尹佩源 ; 赵欣捷 ; 路鑫
- 英文论文作者：Guowang Xu ; Peng Gao ; Yang Liu ; Peiyuan Yin ; Xinjie Zhao ; Xin Lu ; Key Laboratory of Separation Science for Analytical Chemistry ; Dalian Institute of Chemical Physics ; Chinese Academy of Sciences
- 年：2016
- 作者机构：中国科学院大连化学物理研究所中国科学院分离分析化学重点实验室;
- 论文关键词：代谢组学 ; 胶质瘤 ; 亚牛磺酸
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十三分会：复杂样品分离分析
- 语种：中文
- 分类号：R739.41
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十三分会 ; 复杂样品分离分析
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：118k
- 原文格式：D
- 会议级别：全国
摘要
经过十余年的发展,代谢组学在疾病与健康领域内取得了诸多重大的突破。不仅发现了一些新的代谢标志物,而且也阐明了一些代谢物的新功能。我们经过十余年的研究,目前己可实现对代谢组的高覆盖度(~3000种代谢物)、高通量(~100样本/天)以及大规模(>1000样本/批)的分析。在此基础上,我们也发展了基于稳定同位素标记的通量分析的新技术,并整合了分子生物学平台,使关键代谢物的发现与其功能解释得以同步实现。作为功能代谢组学研究的典型例子,我们利用毛细管电泳-质谱技术,发现瘤组织中的关键代谢物亚牛磺酸与胶质瘤恶性程度呈正相关,分子相互作用模拟及分子生物学结果表明,亚牛磺酸能够竞争性抑制脯氨酸羟化酶2活性,导致缺氧诱导因子-1α不降解,进而启动肿瘤相关基因表达。后续的分子、细胞及动物实验确证了亚牛磺酸是目前新发现的又一具有促癌特征的代谢物,其底物牛磺酸则能抑制胶质瘤生长。这一结果对胶质瘤的临床治疗及药物开发具有重要意义。
Functional metabolomics focuses on the biological roles of key metabolites during the development of diseases.Based on our robust analytical platform of metabolomics,we have established a systemic strategy for functional understanding of metabolites including stable isotope label-based flux analysis and molecular biology.A typical functional metabolomics study will be presented in this lecture.A key metabolite,hypotaurine,identified from metabolomics study of glioma indicated that tissue hypotaurine level was strongly and positively correlated with glioma grade.Functional studies in vitro indicated that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2,which was directly correlated with high malignance of glioma.And animal experiments indicated that taurine,the substrate of hypotaurene,could act as an inhibitor preventing the fast development of glioma.As a newly found oncometabolite,hypotaurine could act as a new target for the diagnosis and treatment of glioma.
Functional metabolomics focuses on the biological roles of key metabolites during the development of diseases.Based on our robust analytical platform of metabolomics,we have established a systemic strategy for functional understanding of metabolites including stable isotope label-based flux analysis and molecular biology.A typical functional metabolomics study will be presented in this lecture.A key metabolite,hypotaurine,identified from metabolomics study of glioma indicated that tissue hypotaurine level was strongly and positively correlated with glioma grade.Functional studies in vitro indicated that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2,which was directly correlated with high malignance of glioma.And animal experiments indicated that taurine,the substrate of hypotaurene,could act as an inhibitor preventing the fast development of glioma.As a newly found oncometabolite,hypotaurine could act as a new target for the diagnosis and treatment of glioma.
引文
[1]Gao P,Yang C,Nesvick CL,Feldman MJ,Sizdahkhani S,Liu H,Chu H,Yang F,Tang L,Tian J,Zhao S,Li G,Heiss JD,Liu Y,Zhuang Z,Xu G.Oncotarget.2016,doi:10.18632/oncotarget.7710.
[2]Zhao Y,Hao Z,Zhao C,Zhao J,Zhang J,Li Y,Li L,Huang X,Lin X,Zeng Z,Lu X,Xu G.Anal Chem.2016,88:2234-42.
[2]Zhao Y,Hao Z,Zhao C,Zhao J,Zhang J,Li Y,Li L,Huang X,Lin X,Zeng Z,Lu X,Xu G.Anal Chem.2016,88:2234-42.