TY - JOUR
T1 - MZF-1/Elk-1 complex binds to protein kinase Cα promoter and is involved in hepatocellular carcinoma
AU - Yue, Chia Herng
AU - Huang, Chih Yang
AU - Tsai, Jen Hsiang
AU - Hsu, Chih Wei
AU - Hsieh, Yi Hsien
AU - Lin, Ho
AU - Liu, Jer Yuh
N1 - Publisher Copyright:
© 2015 Yue et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/5
Y1 - 2015/5
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0127420
DO - 10.1371/journal.pone.0127420
M3 - Article
C2 - 26010542
AN - SCOPUS:84960089213
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 5
M1 - e0127420
ER -