Journal of Molecular Cell Biology杂志近日在线发表了生化与细胞所吴家睿研究组与陈洛南研究组共同合作取得的研究成果，报道了一种细胞环境对p53分子调控网络的影响机制及其在肿瘤发生中的作用。
细胞的各种活动，如细胞增殖、分化和凋亡等不是互不相关的孤立过程，而是紧密联系、高度协调的互动过程，这些活动之间需要复杂的分子网络进行协调。并且，每个基因的活动也受到与其形成相互作用的分子网络的影响。以肿瘤为例，越来越多的研究发现，很多原癌基因和肿瘤抑制基因的功能，在肿瘤发生发展的不同条件和阶段有着很大差异。
利用之前景乃禾研究组建立的P19细胞神经分化系统，作者发现被认为能够抑制肿瘤的DNA甲基化抑制剂5-aza-2’-deoxycytidine (ZdCyd)能够干扰分化，并且使得分化过程中悬浮生长的P19细胞获得异常的增殖能力。通过转录因子活性网络分析，作者确定了被ZdCyd激活的p53在贴壁状态（分化前）和悬浮状态（分化中）执行了不同的功能，使得药物对于P19细胞的增殖产生了不同的影响。蛋白质相互作用网络分析揭示，p53的功能是由其所处在的细胞内分子网络所决定的。利用siRNA方法抑制p53的表达后，作者发现在悬浮条件下加入ZdCyd的P19细胞没有成瘤能力，证实了之前的系统生物学分析。
该研究工作得到国家自然科学基金委和科技部的经费资助。（生物谷Bioon.com）
doi:10.1093/jmcb/mjs022
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Systems biology for complex diseases
Luonan Chen，Jiarui Wu
Systems biology views a living organism as an interacting and dynamical network of genes, proteins, and biochemical reactions which give rise to the function and behavior of that organism, and is considered as a powerfully analytical approach to reveal the essential mechanisms of initiation and progression for complex diseases such as cancer, cardiovascular disease, and diabetes. The classical bio-medicine based on molecular biology, cell biology, genetics, and other experimental biology has made significant progress against diseases in general. However, the researchers on the bio-medicine area still face the great challenge against the complex diseases, since the methodology of the classical experimental biology is mainly based on studying individual genes and proteins and treating organisms as simple and linear systems, which are not good enough to solve increasingly complicated problems of the diseases. Therefore, the methodologies and techniques of systems biology are strongly demanded for analyzing the molecular mechanisms of the complex diseases and providing new solutions to fight the complex diseases.
