scholarly journals E2F and GATA switches turn off WD repeat domain 77 expression in differentiating cells

2016 ◽  
Vol 473 (15) ◽  
pp. 2331-2343 ◽  
Author(s):  
Min Yu ◽  
Ulrica Wang ◽  
Zhengxin Wang
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Lung Development ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Lung Tumorigenesis ◽  
Repeat Domain ◽  
Gel Shift Assay ◽  
Bona Fide ◽  
Wd Repeat

WDR77 (WD repeat domain 77) is expressed during earlier lung development when cells are rapidly proliferating, but is absent from adult lung. It is re-activated during lung tumorigenesis and is essential for lung cancer cell proliferation. Signalling pathways/molecules that control WDR77 gene expression are unknown. Promoter mapping, gel shift assay and ChIP revealed that the WDR77 promoter contains bona fide response elements for E2F and GATA transcriptional factors as demonstrated in prostate cancer, lung cancer and erythroid cells, as well as in mouse lung tissues. The WDR77 promoter is transactivated by E2F1, E2F3, GATA1 and GATA6, but suppressed by E2F6, GATA1 and GATA3 in prostate cancer PC3 cells. WDR77 expression is associated with E2F1, E2F3, GATA2 and GATA6 occupancy on the WDR77 gene, whereas, in contrast, E2F6, GATA1 and GATA3 occupancy is associated with the loss of WDR77 expression during erythroid maturation and lung development. More importantly, the loss of WDR77 expression that results from E2F and GATA switches is required for cellular differentiation of erythroid and lung epithelial cells. In contrast, lung cancer cells avoid post-mitotic differentiation by sustaining WDR77 expression. Altogether, the present study provides a novel molecular mechanism by which WDR77 is regulated during erythroid and lung development and lung tumorigenesis.

scholarly journals WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer

Theranostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 4809-4824
Author(s):  
Qianghua Zhou ◽  
Xu Chen ◽  
Haixia He ◽  
Shengmeng Peng ◽  
Yangjie Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Repeat Domain ◽  
Wd Repeat

scholarly journals Ex vivo model of non‑small cell lung cancer using mouse lung epithelial cells

2017 ◽  
Author(s):  
Taku Sato ◽  
Mami Morita ◽  
Ryota Tanaka ◽  
Yui Inoue ◽  
Miyuki Nomura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Cells ◽  
Small Cell Lung Cancer ◽  
Ex Vivo ◽  
Small Cell ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Small Cell Lung ◽  
Ex Vivo Model ◽  
Lung Epithelial

scholarly journals WD Repeat Domain 77 Protein Regulates Translation of E2F1 and E2F3 mRNA

2020 ◽  
Vol 40 (24) ◽  
Author(s):  
Mahmood Anber Altayyar ◽  
Xiumei Sheng ◽  
Zhengxin Wang
Keyword(s):  
Cell Growth ◽  
Translational Regulation ◽  
Cellular Proliferation ◽  
Inhibitory Effect ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Lung Tumorigenesis ◽  
Prostate Tumorigenesis ◽  
Repeat Domain ◽  
Wd Repeat

ABSTRACT WD repeat domain 77 protein (WDR77) is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is reactivated during prostate and lung tumorigenesis. WDR77 plays an essential role in prostate tumorigenesis and cell growth mediated by growth regulatory factors. Here, we identified E2F1 and E2F3 mRNAs as translational targets of WDR77. We demonstrated that WDR77 regulated the translation of E2F1 and E2F3 mRNAs through the 5′ untranslated regions (UTRs) of E2F1 and E2F3 (E2F1/3) mRNAs. WDR77 physically interacted with programmed cell death 4 (PDCD4) that suppresses translation of mRNAs containing structured 5′ UTRs by interacting with eukaryotic translation initiation factor 4A (eIF4A) and inhibiting its helicase activity. Further, we demonstrated that the interaction between WDR77 and PDCD4 prevented the binding of PDCD4 to eIF4A and relieved PDCD4's inhibitory effect on eIF4A1. Overall, our work reveals for the first time that WDR77 is directly involved in translational regulation of E2F1/3 mRNAs through their structured 5′ UTRs, PDCD4, and eIF4A1 and provides novel insight into the cell growth controlled by WDR77.

scholarly journals M2 macrophages‐derived exosomal microRNA-501-3p promotes the progression of lung cancer via targeting WD repeat domain 82

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jie Lei ◽  
Peng Chen ◽  
Feng Zhang ◽  
Na Zhang ◽  
Jianfei Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Cancer Tissue ◽  
M2 Macrophages ◽  
Repeat Domain ◽  
Predictive Role ◽  
Wd Repeat ◽  
Tissue Specimens ◽  
Cancer Tissues

Abstract Background Exosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82). Methods Lung cancer tissue and normal tissue specimens were collected, in which tumor-associated macrophages (TAM) were measured by immunohistochemistry. M2 macrophages were induced and treated with altered miR-501-3p, and then the exosomes were extracted and identified. MiR-501-3p and WDR82 expression in LC tissues and cell liens was determined. The predictive role of miR-501-3p in prognosis of LC patients was assessed, and the proliferation, colony formation ability, invasion, migration and apoptosis of the LC cells were determined. Targeting relationship between miR-501-3p and WDR82 was confirmed. Results TAM level was elevated in lung cancer tissues. MiR-501-3p was upregulated while WDR82 was downregulated in LC tissues and cell lines, and the M2 exosomes further upregulated miR-501-3p. M2 exosomes and exosomal miR-501-3p promoted LC cell growth. MiR-501-3p inhibition reversed the effect of M2 exosomes on LC cells. WDR82 was confirmed as a target gene of miR-501-3p. Conclusion M2 macrophages-derived exosomal miR-501-3p promotes the progression of LC via downregulating WDR82.

scholarly journals Effect of Slit/Robo signaling on regeneration in lung emphysema

2021 ◽  
Author(s):  
Jin-Soo Park ◽  
RyeonJin Cho ◽  
Eun-Young Kang ◽  
Yeon-Mok Oh
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Irreversible Damage ◽  
Lung Epithelial ◽  
And Migration ◽  
Proliferation And Migration

AbstractEmphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema.

scholarly journals DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model

Gene Therapy ◽  
2014 ◽  
Vol 21 (10) ◽  
pp. 888-896 ◽  
Author(s):  
T-Y Weng ◽  
M-C Yen ◽  
C-T Huang ◽  
J-J Hung ◽  
Y-L Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transgenic Mouse ◽  
Dna Vaccine ◽  
Mouse Lung ◽  
Cancer Model ◽  
Antitumor Response ◽  
Lung Cancer Model
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