Abstract
Except for biochemical effects, suspension state (Sus) is proved to induce epithelial-mesenchymal transition (EMT) of circulating tumor cells (CTCs) mechanically. However, the difference between the effects of the mechanical microenvironment in capillaries (simplified as shear stress (SS) and Sus) and single Sus on EMT is unclear, nor the underlying mechanism. Here, breast tumor cells (BTCs) were loaded with Sus and SS to mimic the situation of CTCs stimulated by these two kinds of mechanics. It was demonstrated that the EMT of BTCs was enhanced by Sus and SS and the mechanotransductor yes-associated protein (YAP) was partially cytoplasmic stored with microRNA (miR)-29b decreased, which was detected by miR sequencing. Though it couldn’t possess a feedback regulation, YAP promoted miR-29b expression and posttranscriptionally regulated BTCs EMT through miR-29b, where transforming growth factor β involved. Analysis of clinical database showed that high miR-29b expression was beneficial to high survival rate stabilizing its role of tumor suppressor. This study discovers the mechanism that Sus and SS promote BTCs EMT by YAP through miR-29b posttranscriptionally and highlight the potential of YAP and miR-29b in tumor therapy.
Graphical abstract
The combination of suspension state and shear stress promotes transforming growth factor β involved epithelial-mesenchymal transition by yes-associated protein through microRNA-29b
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors thank Dr. Xiaomei Zhang for getting miR sequencing results of MDA-MB-231 cells.
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This work was supported by National Natural Science Foundation of China (11872134, 11672051), Natural Science Foundation of Chongqing, China (cstc2020jcyj-msxmX0035) and sharing fund of Chongqing university's large-scale equipment (202103150042).
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Conceptualization, formal analysis, investigation, methodology, writing — original draft — was made by Boyuan Zhao. Conceptualization, investigation, methodology, data curation, formal analysis, supervision, funding acquisition, investigation, methodology, project administration, writing — review and editing — were performed by Yonggang Lv.
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Zhao, B., Lv, Y. Suspension state and shear stress enhance breast tumor cells EMT through YAP by microRNA-29b. Cell Biol Toxicol 39, 1037–1052 (2023). https://doi.org/10.1007/s10565-021-09661-6
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DOI: https://doi.org/10.1007/s10565-021-09661-6