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基于网络的癌症细胞凋亡信号通路间新连接的识别。

Network-based identification of novel connections among apoptotic signaling pathways in cancer.

机构信息

School of Life Sciences and The State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610064, China.

出版信息

Appl Biochem Biotechnol. 2012 Jun;167(3):621-31. doi: 10.1007/s12010-012-9704-x. Epub 2012 May 12.

DOI:10.1007/s12010-012-9704-x
PMID:22581077
Abstract

MicroRNAs (miRNAs), highly conserved, non-coding endogenous RNA and nearly ~22 nucleotides (nt) in length, are well-known to regulate several apoptotic pathways in cancer. In this study, we computationally constructed the initial human apoptotic PPI network by several online databases, and further integrated these high-throughput datasets into a Naïve Bayesian model to predict protein functional connections. Based on the modified apoptotic network, we identified several apoptotic hub proteins such as TP53, SRC, M3K3/5/8, cyclin-dependent kinase2/6, TNFR16/19, and TGF-β receptor 1/2. Subsequently, we identified some microRNAs that could target the aforementioned apoptotic hub proteins by using TargetScan, PicTar, and Diana-MicroH. In conclusion, these results demonstrate the PPI network-based identification of new connections amongst apoptotic pathways in cancer, which may shed new light on the intricate relationships between core apoptotic pathways and some targeted miRNAs in human cancers.

摘要

微小 RNA(miRNAs)是高度保守的非编码内源性 RNA,长度约为 22 个核苷酸(nt),已知可调节癌症中的几种凋亡途径。在这项研究中,我们通过几个在线数据库计算构建了初始的人类凋亡 PPI 网络,并进一步将这些高通量数据集整合到一个朴素贝叶斯模型中,以预测蛋白质的功能连接。基于修改后的凋亡网络,我们鉴定了一些凋亡枢纽蛋白,如 TP53、SRC、M3K3/5/8、细胞周期蛋白依赖性激酶 2/6、TNFR16/19 和 TGF-β 受体 1/2。随后,我们使用 TargetScan、PicTar 和 Diana-MicroH 鉴定了一些可以靶向上述凋亡枢纽蛋白的 microRNAs。总之,这些结果表明,基于 PPI 网络的方法可以识别癌症中凋亡途径之间的新连接,这可能为核心凋亡途径与人类癌症中的某些靶向 microRNAs 之间的复杂关系提供新的见解。

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