NDLI: A possible role for epigenetic feedback regulation in the dynamics of the epithelial

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A possible role for epigenetic feedback regulation in the dynamics of the epithelial–mesenchymal transition (EMT)

Content Provider	Scilit
Author	Jia, Wen Deshmukh, Abhijeet Mani, Sendurai A. Jolly, Mohit Kumar Levine, Herbert
Copyright Year	2019
Description	Journal: Physical Biology The epithelial-mesenchymal transition (EMT) often plays a critical role in cancer metastasis and chemoresistance, and decoding its dynamics is crucial to design effective therapeutics. EMT is regulated at multiple levels-transcriptional, translational, protein stability and epigenetics; the mechanisms by which epigenetic regulation can alter the dynamics of EMT remain elusive. Here, to identify the possible effects of epigenetic regulation in EMT, we incorporate a feedback term in our previously proposed model of EMT regulation of the miR-200/ZEB/miR-34/SNAIL circuit. This epigenetic feedback that stabilizes long-term transcriptional activity can alter the relative stability and distribution of states in a given cell population, particularly when incorporated in the inhibitory effect on miR-200 from ZEB. This feedback can stabilize the mesenchymal state, thus making transitions out of that state difficult. Conversely, epigenetic regulation of the self-activation of ZEB has only minor effects. Our model predicts that this effect could be seen in experiments, when epithelial cells are treated with an external EMT-inducing signal for a sufficiently long period of time and then allowed to recover. Our preliminary experimental data indicates that a chronic TGF-β exposure gives rise to irreveversible EMT state; i.e. unable to reverse back to the epithelial state. Thus, this integrated theoretical-experimental approach yields insights into how an epigenetic feedback may alter the dynamics of EMT.
Related Links	http://eprints.iisc.ac.in/63668/2/PBab334df_supplementarymaterial.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085921/pdf
Ending Page	066004
Page Count	1
Starting Page	066004
ISSN	14783967
e-ISSN	14783975
DOI	10.1088/1478-3975/ab34df
Journal	Physical Biology
Issue Number	6
Volume Number	16
Language	English
Publisher	IOP Publishing
Publisher Date	2019-09-06
Access Restriction	Open
Subject Keyword	Journal: Physical Biology Mathematical and Computational Biology Epithelial-mesenchymal Transition Mathematical Modeling Epigenetic Regulation
Content Type	Text
Resource Type	Article
Subject	Cell Biology Structural Biology Molecular Biology Biophysics

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