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10.1158/0008-5472.CAN-16-0512

http://scihub22266oqcxt.onion/10.1158/0008-5472.CAN-16-0512
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suck abstract from ncbi


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pmid28087598
      Cancer+Res 2017 ; 77 (7 ): 1575-1585
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  • Bayesian Network Inference Modeling Identifies TRIB1 as a Novel Regulator of Cell-Cycle Progression and Survival in Cancer Cells #MMPMID28087598
  • Gendelman R ; Xing H ; Mirzoeva OK ; Sarde P ; Curtis C ; Feiler HS ; McDonagh P ; Gray JW ; Khalil I ; Korn WM
  • Cancer Res 2017[Apr]; 77 (7 ): 1575-1585 PMID28087598 show ga
  • Molecular networks governing responses to targeted therapies in cancer cells are complex dynamic systems that demonstrate nonintuitive behaviors. We applied a novel computational strategy to infer probabilistic causal relationships between network components based on gene expression. We constructed a model comprised of an ensemble of networks using multidimensional data from cell line models of cell-cycle arrest caused by inhibition of MEK1/2. Through simulation of a reverse-engineered Bayesian network model, we generated predictions of G(1)-S transition. The model identified known components of the cell-cycle machinery, such as CCND1, CCNE2, and CDC25A, as well as revealed novel regulators of G(1)-S transition, IER2, TRIB1, TRIM27. Experimental validation of model predictions confirmed 10 of 12 predicted genes to have a role in G(1)-S progression. Further analysis showed that TRIB1 regulated the cyclin D1 promoter via NF?B and AP-1 sites and sensitized cells to TRAIL-induced apoptosis. In clinical specimens of breast cancer, TRIB1 levels correlated with expression of NF?B and its target genes (IL8, CSF2), and TRIB1 copy number and expression were predictive of clinical outcome. Together, our results establish a critical role of TRIB1 in cell cycle and survival that is mediated via the modulation of NF?B signaling. Cancer Res; 77(7); 1575-85. ©2017 AACR.
  • |*Cell Cycle [MESH]
  • |Bayes Theorem [MESH]
  • |Breast Neoplasms/drug therapy/genetics/*pathology [MESH]
  • |Cell Line, Tumor [MESH]
  • |Cell Survival [MESH]
  • |Cyclin D1/genetics [MESH]
  • |Female [MESH]
  • |Humans [MESH]
  • |Intracellular Signaling Peptides and Proteins/genetics/*physiology [MESH]
  • |Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors [MESH]
  • |NF-kappa B/physiology [MESH]
  • |Phosphatidylinositol 3-Kinases/physiology [MESH]
  • |Promoter Regions, Genetic [MESH]
  • |Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics/physiology [MESH]
  • |Proto-Oncogene Proteins c-akt/physiology [MESH]


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