distinct and competitive regulatory patterns of tumor suppressor genes and oncogenes in ovarian cancer不同的监管模式和竞争卵巢癌的肿瘤抑制基因和致癌基因.pdfVIP

Distinct and Competitive Regulatory Patterns of Tumor Suppressor Genes and Oncogenes in Ovarian Cancer 1 1 1,2,3,4 Min Zhao , Jingchun Sun , Zhongming Zhao * 1 Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 2 Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 3 Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 4 Center for Quantitative Sciences, Vanderbilt University, Nashville, Tennessee, United States of America Abstract Background: So far, investigators have found numerous tumor suppressor genes (TSGs) and oncogenes (OCGs) that control cell proliferation and apoptosis during cancer development. Furthermore, TSGs and OCGs may act as modulators of transcription factors (TFs) to influence gene regulation. A comprehensive investigation of TSGs, OCGs, TFs, and their joint target genes at the network level may provide a deeper understanding of the post-translational modulation of TSGs and OCGs to TF gene regulation. Methodology/Principal Findings: In this study, we developed a novel computational framework for identifying target genes of TSGs and OCGs using TFs as bridges through the integration of protein-protein interactions and gene expression data. We applied this pipeline to ovarian cancer and constructed a three-layer regulatory network. In the network, the top layer was comprised of modulators (TSGs and OCGs), the middle layer included TFs, and the bottom layer contained target genes. Based on regulatory relationships in the network, we compiled TSG and OCG profiles and performed clustering analy