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

Abstract

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.

Hypoxia/Inflammation-Induced Upregulation of HIF-1α and C/EBPβ, Promoted Nephroblastoma EMT by Improving HOXA11-AS Transcription

“…C/EBPβ is one transcription regulator involves in the cell cycle of G2/M [30] [35] demonstrated that knockdown C/EBPβ reduces in ammation, which is consistent with our present study. In ammationinduced miR-155 and inhibits the self-renewal of neural stem cells through suppressing the expression of C/EBPβ [36].…”

rs822336 binding to C/EBPβ and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC

“…Specifically, we show that in presence of allele C in rs822336, PD-L1 transcription is regulated by the binding of both C/EBPβ and NFIC. In contrast, only C/EBPβ regulates PD-L1 transcription in presence of allele G. C/EBPβ is a TF that promotes the expression of many genes involved in several cellular processes such as apoptosis, cell differentiation, inflammation and tumorigenesis [ 81 , 82 ]. In contrast, NFIC is a TF involved in chromatin remodeling and epigenetic modulation by acting as activator or repressor of gene expression [ 83 ].…”

Knockdown of lncRNA X inactive specific transcript (XIST) radiosensitizes non-small cell lung cancer (NSCLC) cells through regulation of miR-16-5p/WEE1 G2 checkpoint kinase (WEE1) axis

“…Previous studies indicate that XIST, miR-16-5p, WEE1 figure prominently in regulating the development and progression of NSCLC. 17,18,38,39 It is widely accepted that radiotherapy is currently one of the most effective methods for the treatment of a variety of advanced malignancies, including NSCLC. 2,40 However, the effect of radiotherapy is not satisfactory due to the reduced sensitivity of NSCLC cells to X-rays.…”