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UHRF1-KAT7-mediated regulation of TUSC3 expression via histone methylation/acetylation is critical for the proliferation of colon cancer cells

Abstract

The epigenetic factor UHRF1 regulates transcription by modulating DNA methylation and histone modification, and plays critical roles in proliferation, development, and tumorigenesis. Here, we show that Wnt/c-Myc signaling upregulates UHRF1, which in turn downregulates TUSC3, a candidate tumor suppressor gene that is frequently deleted or downregulated in several cancers. We also show that UHRF1-mediated downregulation of TUSC3 is required for the proliferation of colon cancer cells. Furthermore, we demonstrate that UHRF1 suppresses TUSC3 expression by interacting with methylated H3K14 and thereby suppressing the acetylation of H3K14 by the histone acetyltransferase KAT7. Our study provides evidence for the significance of UHRF1-KAT7-mediated regulation of histone methylation/acetylation in the proliferation of tumor cells and in a diverse set of biological processes controlled by Wnt/c-Myc signaling.

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Acknowledgements

This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas (Integrative Analysis and Regulation of Cellular Diversity, no. 17H06325 and Non-coding RNA neo-taxonomy, no. 15H01464) from MEXT, Japan, and Project for Cancer Research and Therapeutic Evolution (P-CREATE, no. 17cm0106103h0002) from the Japan Agency for Medical Research and Development.

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Taniue, K., Hayashi, T., Kamoshida, Y. et al. UHRF1-KAT7-mediated regulation of TUSC3 expression via histone methylation/acetylation is critical for the proliferation of colon cancer cells. Oncogene 39, 1018–1030 (2020). https://doi.org/10.1038/s41388-019-1032-y

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