Dataset Information

Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.

ABSTRACT: To identify regulatory drivers of prostate cancer malignancy, we have assembled genome-wide regulatory networks (interactomes) for human and mouse prostate cancer from expression profiles of human tumors and of genetically engineered mouse models, respectively. Cross-species computational analysis of these interactomes has identified FOXM1 and CENPF as synergistic master regulators of prostate cancer malignancy. Experimental validation shows that FOXM1 and CENPF function synergistically to promote tumor growth by coordinated regulation of target gene expression and activation of key signaling pathways associated with prostate cancer malignancy. Furthermore, co-expression of FOXM1 and CENPF is a robust prognostic indicator of poor survival and metastasis. Thus, genome-wide cross-species interrogation of regulatory networks represents a valuable strategy to identify causal mechanisms of human cancer.

SUBMITTER: Aytes A

PROVIDER: S-EPMC4051317 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.

Aytes Alvaro A Mitrofanova Antonina A Lefebvre Celine C Alvarez Mariano J MJ Castillo-Martin Mireia M Zheng Tian T Eastham James A JA Gopalan Anuradha A Pienta Kenneth J KJ Shen Michael M MM Shen Michael M MM Califano Andrea A Abate-Shen Cory C

Cancer cell 20140501 5

To identify regulatory drivers of prostate cancer malignancy, we have assembled genome-wide regulatory networks (interactomes) for human and mouse prostate cancer from expression profiles of human tumors and of genetically engineered mouse models, respectively. Cross-species computational analysis of these interactomes has identified FOXM1 and CENPF as synergistic master regulators of prostate cancer malignancy. Experimental validation shows that FOXM1 and CENPF function synergistically to promo ...[more]

PMID: 24823640

Similar Datasets

Project description:BackgroundTripterygium hypoglaucum Hutch (THH) both has prominent efficacy and unwarranted toxicity in the treatment of autoimmune diseases. Nevertheless, its pharmacological and toxicological profiles still remain to be elucidated. In the current study, the network pharmacology approach was applied to identify synergistic interaction and mechanism of efficacy and toxicity for THH from a holistic perspective.MethodsThe compounds from THH were collected using literature retrieval and relevant databases. After the production of putative therapeutic targets for dominant diseases and harmful targets of adverse reactions (ADRs) induced by THH, the protein-protein interactions (PPIs), topological analysis and pathway enrichment were established to distinguish the hub targets and pathways. Additionally, the binding activity of candidate ingredients with core targets were revealed by molecular docking simulation.ResultsA total of eight bioactive components in THH were enrolled, and 633 targets were responsible for rheumatoid arthritis (RA), 1067 targets were corresponding to systemic lupus erythematosus (SLE), 1318 targets of ADRs were obtained. The results of enrichment analysis among THH-RA, THH-SLE and THH-ADR networks indicated that pathway in cancer, hepatitis B, rheumatoid arthritis, and PI3K-Akt signaling pathway might participate in THH for treating RA and SLE. Besides, the mechanism of ADRs that induced by THH were associated with viral carcinogenesis, p53 signaling pathway, PI3K-Akt signaling pathway, and so on. Whereas, these active ingredients of THH exerted the superior binding activities with crucial targets including STAT3, VEGFA, TP53 and MMP9 that functioned synergistically efficacy and toxicity as observed via molecular docking simulation.ConclusionThe present research preliminarily interpreted the synergistic interaction of therapeutic and toxicological mechanisms for THH through the comprehensive analysis of relationship and binding activity between primary components and core targets, providing a feasible and promising approach to facilitate the development of toxic and irreplaceable herbs.

Dataset Information

Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.

Publications

Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets