Abstract
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.
Keywords:
KLF5; ZEB2; epithelial-mesenchymal transition; liver cancer; miR-192.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Biomarkers, Tumor / metabolism
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Cell Line, Tumor
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Cell Movement / genetics
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Epithelial-Mesenchymal Transition*
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Gene Expression Regulation, Neoplastic
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Humans
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Kruppel-Like Transcription Factors / metabolism*
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology*
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Models, Biological
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Mutation / genetics
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Neoplasm Invasiveness
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Protein Binding / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Zinc Finger E-box Binding Homeobox 2 / genetics
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Zinc Finger E-box Binding Homeobox 2 / metabolism*
Substances
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Biomarkers, Tumor
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KLF5 protein, human
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Kruppel-Like Transcription Factors
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MIRN192 microRNA, human
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MicroRNAs
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Tumor Suppressor Protein p53
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Zinc Finger E-box Binding Homeobox 2
Grants and funding
This work was supported by the Natural Science Foundation of Beijing Municipality [7202034]; Wang Bao-En Liver Fibrosis Foundation [20181017].