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

Kruppel-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, we find that 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. However, we also find that the regulation of ZEB2 by p53 and KLF5 is indirect and that miR-192 mediates this regulation. Most importantly, we report that miR-192 is directly and differentially bound and regulated by KLF5 and p53 and that forced expression of miR-192 mimics reverses the EMT- promoting effect of KLF5 silencing. Finally, we find that in invasive liver cancer, KLF5 is absent in the context of p53 loss or mutation.