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Open AccessArticle

C/EBPβ Is a Transcriptional Regulator of Wee1 at the G2/M Phase of the Cell Cycle

1
Division of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, Korea
2
Division of Clinical Research, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, Korea
3
Department of Pathology, National Cancer Center, Goyang, Gyeonggido 411-769, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cells 2019, 8(2), 145; https://doi.org/10.3390/cells8020145
Received: 18 January 2019 / Revised: 6 February 2019 / Accepted: 9 February 2019 / Published: 11 February 2019
The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that regulates cellular proliferation, differentiation, apoptosis and tumorigenesis. Although the pro-oncogenic roles of C/EBPβ have been implicated in various human cancers, how it contributes to tumorigenesis or tumor progression has not been determined. Immunohistochemistry with human non-small cell lung cancer (NSCLC) tissues revealed that higher levels of C/EBPβ protein were expressed compared to normal lung tissues. Knockdown of C/EBPβ by siRNA reduced the proliferative capacity of NSCLC cells by delaying the G2/M transition in the cell cycle. In C/EBPβ-knockdown cells, a prolonged increase in phosphorylation of cyclin dependent kinase 1 at tyrosine 15 (Y15-pCDK1) was displayed with simultaneously increased Wee1 and decreased Cdc25B expression. Chromatin immunoprecipitation (ChIP) analysis showed that C/EBPβ bound to distal promoter regions of WEE1 and repressed WEE1 transcription through its interaction with histone deacetylase 2. Treatment of C/EBPβ-knockdown cells with a Wee1 inhibitor induced a decrease in Y15-pCDK1 and recovered cells from G2/M arrest. In the xenograft tumors, the depletion of C/EBPβ significantly reduced tumor growth. Taken together, these results indicate that Wee1 is a novel transcription target of C/EBPβ that is required for the G2/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells. View Full-Text
Keywords: cell cycle; lung cancer; C/EBPβ; G2/M arrest; Wee1; Y15-pCDK1 cell cycle; lung cancer; C/EBPβ; G2/M arrest; Wee1; Y15-pCDK1
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Lee, J.H.; Sung, J.Y.; Choi, E.K.; Yoon, H.-K.; Kang, B.R.; Hong, E.K.; Park, B.-K.; Kim, Y.-N.; Rho, S.B.; Yoon, K. C/EBPβ Is a Transcriptional Regulator of Wee1 at the G2/M Phase of the Cell Cycle. Cells 2019, 8, 145.

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