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KLF5 regulates epithelial-mesenchymal transition of liver cancer cells in the context of p53 loss through miR-192 targeting of ZEB2

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posted on 2020-09-23, 14:20 authored by Lan Sun, Xiaona Zhou, Yanmeng Li, Wei Chen, Shanna Wu, Bei Zhang, Jingyi Yao, Anjian Xu

Krüppel-like factor 5 (KLF5) can both promote and suppress cell migration, but the underlying mechanisms have not been elucidated. In this study, we show that the function of KLF5 in epithelial-mesenchymal transition (EMT) and migration of liver cancer cells depends on the status of the cellular tumor antigen p53 (p53). Furthermore, zinc finger E-box-binding homeobox 2 (ZEB2) is the main regulator of KLF5 in EMT in liver cancer cells in the context of p53 loss. Most importantly, the regulation of ZEB2 by p53 and KLF5 is indirect and that miR-192 mediates this regulation. Finally, we find that in invasive liver cancer, KLF5 is absent in the context of p53 loss or mutation.

Funding

This work was supported by the Natural Science Foundation of Beijing Municipality [7202034]; Wang Bao-En Liver Fibrosis Foundation [20181017].

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