C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle

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 tumo...

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Main Authors:	Ji Hae Lee, Jee Young Sung, Eun Kyung Choi, Hyun-Kyoung Yoon, Bo Ram Kang, Eun Kyung Hong, Byung-Kiu Park, Yong-Nyun Kim, Seung Bae Rho, Kyungsil Yoon
Format:	Article
Language:	English
Published:	MDPI AG 2019-02-01
Series:	Cells
Subjects:	cell cycle lung cancer C/EBPβ G<sub>2</sub>/M arrest Wee1 Y15-pCDK1
Online Access:	https://www.mdpi.com/2073-4409/8/2/145

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spelling	doaj-019489cd7a534d8dbe6c82bce2f8aa7f2020-11-25T00:19:02ZengMDPI AGCells2073-44092019-02-018214510.3390/cells8020145cells8020145C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell CycleJi Hae Lee0Jee Young Sung1Eun Kyung Choi2Hyun-Kyoung Yoon3Bo Ram Kang4Eun Kyung Hong5Byung-Kiu Park6Yong-Nyun Kim7Seung Bae Rho8Kyungsil Yoon9Division of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Clinical Research, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDepartment of Pathology, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Clinical Research, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaDivision of Translational Science, Research Institute, National Cancer Center, Goyang, Gyeonggido 411-769, KoreaThe 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 G<sub>2</sub>/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 <i>WEE1</i> and repressed <i>WEE1</i> 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 G<sub>2</sub>/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 G<sub>2</sub>/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells.https://www.mdpi.com/2073-4409/8/2/145cell cyclelung cancerC/EBPβG<sub>2</sub>/M arrestWee1Y15-pCDK1
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ji Hae Lee Jee Young Sung Eun Kyung Choi Hyun-Kyoung Yoon Bo Ram Kang Eun Kyung Hong Byung-Kiu Park Yong-Nyun Kim Seung Bae Rho Kyungsil Yoon
spellingShingle	Ji Hae Lee Jee Young Sung Eun Kyung Choi Hyun-Kyoung Yoon Bo Ram Kang Eun Kyung Hong Byung-Kiu Park Yong-Nyun Kim Seung Bae Rho Kyungsil Yoon C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle Cells cell cycle lung cancer C/EBPβ G<sub>2</sub>/M arrest Wee1 Y15-pCDK1
author_facet	Ji Hae Lee Jee Young Sung Eun Kyung Choi Hyun-Kyoung Yoon Bo Ram Kang Eun Kyung Hong Byung-Kiu Park Yong-Nyun Kim Seung Bae Rho Kyungsil Yoon
author_sort	Ji Hae Lee
title	C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle
title_short	C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle
title_full	C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle
title_fullStr	C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle
title_full_unstemmed	C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle
title_sort	c/ebpβ is a transcriptional regulator of wee1 at the g<sub>2</sub>/m phase of the cell cycle
publisher	MDPI AG
series	Cells
issn	2073-4409
publishDate	2019-02-01
description	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 G<sub>2</sub>/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 <i>WEE1</i> and repressed <i>WEE1</i> 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 G<sub>2</sub>/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 G<sub>2</sub>/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells.
topic	cell cycle lung cancer C/EBPβ G<sub>2</sub>/M arrest Wee1 Y15-pCDK1
url	https://www.mdpi.com/2073-4409/8/2/145
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C/EBPβ Is a Transcriptional Regulator of Wee1 at the G<sub>2</sub>/M Phase of the Cell Cycle

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