System modeling reveals the molecular mechanisms of HSC cell cycle alteration mediated by Maff and Egr3 under leukemia

Abstract

Background Molecular mechanisms of the functional alteration of hematopoietic stem cells (HSCs) in leukemic environment attract intensive research interests. As known in previous researches, Maff and Egr3 are two important genes having opposite functions on cell cycle; however, they are both highly expressed in HSCs under leukemia. Hence, exploring the molecular mechanisms of how the genes act on cell cycle will help revealing the functional alteration of HSCs. Results We herein utilize the bioinformatic resources to computationally model the acting mechanisms of Maff and Egr3 on cell cycle. Using the data of functional experiments as reference, molecular acting mechanisms are optimally enumerated through model selection. The results are consolidated by evidences from gene sequence analysis, thus having enhanced the confidence of our pilot findings, which suggest that HSCs possibly undergo a “adaptation - suppression” process in response to the malignant environment of leukemia. Conclusion As a pilot research, our results may provide valuable insights for further experimental studies. Meanwhile, our research method combining computational modeling and data from functional experiments can be worthwhile for knowledge discovery; and it can be generalized and extended to other biological/biomedical studies. Electronic supplementary material The online version of this article (doi:10.1186/s12918-017-0467-4) contains supplementary material, which is available to authorized users.