Research Papers:

Changes of signal transductivity and robustness of gene regulatory network in the carcinogenesis of leukemic subtypes via microarray sample data

Cheng-Wei Li, Tzu-Ying Lai and Bor-Sen Chen _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:23636-23660. https://doi.org/10.18632/oncotarget.25318

Metrics: PDF 519 views  |   HTML 955 views  |   ?  


Cheng-Wei Li1, Tzu-Ying Lai1 and Bor-Sen Chen1

1Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan

Correspondence to:

Bor-Sen Chen, email: bschen@ee.nthu.edu.tw

Keywords: transductivity; network robustness; transductivity sensitivity; error sensitivity; basal sensitivity

Received: November 11, 2016     Accepted: April 11, 2018     Published: May 04, 2018


Mutation accumulation and epigenetic alterations in genes are important for carcinogenesis. Because leukemogenesis-related signal pathways have been investigated and microarray sample data have been produced in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and normal cells, systems analysis in coupling pathways becomes possible.

Based on system modeling and identification, we could construct the coupling pathways and their associated gene regulatory networks using microarray sample data. By applying system theory to the estimated system model in coupling pathways, we can then obtain transductivity sensitivity, basal sensitivity and error sensitivity of each protein to identify the potential impact of genetic mutations, epigenetic alterations and the coupling of other pathways from the perspective of energy, respectively. By comparing the results in AML, MDS and normal cells, we investigated the potential critical genetic mutations and epigenetic alterations that activate or repress specific cellular functions to promote MDS or AML leukemogenesis. We suggested that epigenetic modification of β-catenin and signal integration of CSLs, AP-2α, STATs, c-Jun and β-catenin could contribute to cell proliferation at AML and MDS. Epigenetic regulation of ERK and genetic mutation of p53 could lead to the repressed apoptosis, cell cycle arrest and DNA repair in leukemic cells. Genetic mutation of JAK, epigenetic regulation of ERK, and signal integration of C/EBPα could result in the promotion of MDS cell differentiation. According to the results, we proposed three drugs, decitabine, genistein, and monorden for preventing AML leukemogenesis, while three drugs, decitabine, thalidomide, and geldanamycin, for preventing MDS leukemogenesis.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 25318