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Network-Based Identification of Novel Connections Among Apoptotic Signaling Pathways in Cancer
Authors:Nan Wang  Huai-long Xu  Xu Zhao  Xin Wen  Feng-tian Wang  Shu-ya Wang  Lei-lei Fu  Bo Liu  Jin-ku Bao
Institution:1. School of Life Sciences and The State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610064, China
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 Na?ve 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-?? 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.
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