Journal of Molecular Cell Biology雜志近日在線發(fā)表了生化與細胞所吳家睿研究組與陳洛南研究組共同合作取得的研究成果，報道了一種細胞環(huán)境對p53分子調(diào)控網(wǎng)絡(luò)的影響機制及其在腫瘤發(fā)生中的作用,。
細胞的各種活動,，如細胞增殖、分化和凋亡等不是互不相關(guān)的孤立過程,，而是緊密聯(lián)系,、高度協(xié)調(diào)的互動過程，這些活動之間需要復(fù)雜的分子網(wǎng)絡(luò)進行協(xié)調(diào),。并且,，每個基因的活動也受到與其形成相互作用的分子網(wǎng)絡(luò)的影響。以腫瘤為例,，越來越多的研究發(fā)現(xiàn),，很多原癌基因和腫瘤抑制基因的功能,，在腫瘤發(fā)生發(fā)展的不同條件和階段有著很大差異。
利用之前景乃禾研究組建立的P19細胞神經(jīng)分化系統(tǒng),，作者發(fā)現(xiàn)被認為能夠抑制腫瘤的DNA甲基化抑制劑5-aza-2’-deoxycytidine (ZdCyd)能夠干擾分化,，并且使得分化過程中懸浮生長的P19細胞獲得異常的增殖能力。通過轉(zhuǎn)錄因子活性網(wǎng)絡(luò)分析,，作者確定了被ZdCyd激活的p53在貼壁狀態(tài)（分化前）和懸浮狀態(tài)（分化中）執(zhí)行了不同的功能,，使得藥物對于P19細胞的增殖產(chǎn)生了不同的影響。蛋白質(zhì)相互作用網(wǎng)絡(luò)分析揭示,，p53的功能是由其所處在的細胞內(nèi)分子網(wǎng)絡(luò)所決定的,。利用siRNA方法抑制p53的表達后，作者發(fā)現(xiàn)在懸浮條件下加入ZdCyd的P19細胞沒有成瘤能力,，證實了之前的系統(tǒng)生物學(xué)分析,。
該研究工作得到國家自然科學(xué)基金委和科技部的經(jīng)費資助。（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.
