MZF-1/Elk-1 complex binds to protein kinase Cα promoter and is involved in hepatocellular carcinoma

Chia Herng Yue, Chih Yang Huang, Jen Hsiang Tsai, Chih Wei Hsu, Yi Hsien Hsieh, Ho Lin, Jer Yuh Liu

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11 Scopus citations

Abstract

In this study, the molecular mechanism of protein kinase C alpha (PKCα) gene regulation in hepatocellular carcinoma (HCC) involving Ets-like protein-1 (Elk-1) and myeloid zinc finger- 1 (MZF-1) was investigated. The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity, and the transcriptional activity decreased when the transfection included a DNA-binding-deficient (ΔDBD) gene vector of either MZF-1 or Elk-1 DNA-binding deficiency (MZF-1ΔDBD or Elk-1ΔDBD), thereby indicating that the enhanced expression of PKCα was caused by the binding of MZF-1 and/or Elk-1 with the PKCα promoter. We investigated MZF-1 and Elk-1 to determine whether they bind to each other. The results of immunoprecipitation (IP), Co-IP, chromatin IP (ChIP), and Re-ChIP analyses indicated that Elk-1 can directly bind to the N-terminal region of MZF-1 and MZF-1 can directly bind to the C-terminal region of Elk-1 to form a complex before attaching to the PKCα promoter. Furthermore, when MZF-1ΔDBD or Elk-1ΔDBD was added to the cells, PKCα expression decreased, and cell proliferation, migration, invasion, and tumorigenicity also decreased. These findings suggest that PKCα expression in HCC could be stimulated by the formation of MZF-1/Elk-1 complex, which directly binds to the PKCα promoter.

Original languageEnglish (US)
Article numbere0127420
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yue, C. H., Huang, C. Y., Tsai, J. H., Hsu, C. W., Hsieh, Y. H., Lin, H., & Liu, J. Y. (2015). MZF-1/Elk-1 complex binds to protein kinase Cα promoter and is involved in hepatocellular carcinoma. PloS one, 10(5), [e0127420]. https://doi.org/10.1371/journal.pone.0127420