scholarly journals Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression

2018 ◽  
Author(s):  
Huan-Chieh Cho ◽  
Yenlin Huang ◽  
Jung-Tung Hung ◽  
Li-Chun Lai ◽  
Sheng-Hung Wang ◽  
...  

AbstractWe describe a novel biogenesis factor of the 90S pre-ribosome, Puf-A, which is a negative transcriptional target of p53. The expression of Puf-A is not only upregulated in advanced human lung cancer and tumors of patients especially with TP53 mutation, but also is highly prognostic for stage I lung cancer. Loss of Puf-A expression prevents KrasG12D/p53-/-–induced tumor progression in the lungs and induces apoptosis in TP53– mutated cancers and c-Myc/p53-/-–transformed cells as well. Overexpression of Puf-A enhances proliferation of normal cells after c-Myc induction and overcomes the cell-cycle checkpoints incurred by p53 expression. Mechanistically, Puf-A interacts with double-stranded structures of the 5.8S sequence within pre-rRNA and maintains the integrity of 90S pre-ribosomes, thereby impacting early ribosome assembly and export of ribosomes from nuclei. Silencing of Puf-A disrupts the assembly of 90S pre-ribosomes and induces the translocation of its associated nucleophosmin (NPM1) from nucleoli to the nucleoplasm, resulting in impairment of ribosome synthesis. Thus, Puf-A is crucial for over-activation of ribosome biogenesis and contributes to tumor progression and cancer growth.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.


2011 ◽  
Author(s):  
Sandra D. Castillo ◽  
Pedro P. Medina ◽  
Niccolò Mariani ◽  
Montse Sanchez-Cespedes

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Olga V. Kovaleva ◽  
Daniil Romashin ◽  
Irina B. Zborovskaya ◽  
Mikhail M. Davydov ◽  
Murat S. Shogenov ◽  
...  

Recent research on cancer-associated microbial communities led to the accumulation of data on the interplay between bacteria, immune and tumor cells, the pathways of bacterial induction of carcinogenesis, and its meaningfulness for medicine. Microbial communities that have any kind of impact on tumor progression and microorganisms associated with tumors have been defined as oncobiome. Over the last decades, a number of studies were dedicated to Helicobacter pylori and its role in the progression of stomach tumors, so this correlation can be regarded as proven. Involvement of bacteria in the induction of lung cancer has been largely ignored for a long time, though some correlations between this type of cancer and lung microbiome were established. Despite the fact that in the present the microbial impact on lung cancer progression has many confirmations, the underlying mechanisms are poorly understood. Microorganisms can contribute to tumor initiation and progression through production of bacteriotoxins and other proinflammatory factors. The purpose of this review is to organize the available data on lung cancer microbiome and its role in malignant tumor progression.


2011 ◽  
Vol 108 (17) ◽  
pp. 7004-7009 ◽  
Author(s):  
Q. Wei ◽  
H. Jiang ◽  
Z. Xiao ◽  
A. Baker ◽  
M. R. Young ◽  
...  

2009 ◽  
Vol 15 (4) ◽  
pp. 623-630 ◽  
Author(s):  
Tao Ren ◽  
Lin Xu ◽  
Shuxian Jiao ◽  
Yanying Wang ◽  
Yingyun Cai ◽  
...  

Author(s):  
Sarah Neidler ◽  
Björn Kruspig ◽  
Kay Hewit ◽  
Tiziana Monteverde ◽  
Katarina Gyuraszova ◽  
...  

Inducible genetically defined mouse models of cancer uniquely facilitate the investigation of early events in cancer progression, however there are valid concerns about the ability of such models to faithfully recapitulate human disease.  We developed an inducible mouse model of progressive lung adenocarcinoma (LuAd) that combines sporadic activation of oncogenic KRasG12D with modest overexpression of c-MYC (KM model). Histological examination revealed a highly reproducible transition from adenoma to locally invasive adenocarcinoma within 6 weeks of oncogene activation.  Laser-capture microdissection coupled with RNA-SEQ was employed to determine transcriptional changes associated with tumour progression.  Upregulated genes were triaged for relevance to human LuAd using datasets from Oncomine and cBioportal.  Selected genes were validated by RNAi screening in human lung cancer cell lines and examined for association with lung cancer patient overall survival using KMplot.com.  Depletion of progression-associated genes resulted in pronounced viability and/or cell migration defects in human lung cancer cells.  Progression-associated genes moreover exhibited strong associations with overall survival, specifically in human lung adenocarcinoma, but not in squamous cell carcinoma. The KM mouse model faithfully recapitulates key molecular events in human lung cancer and is a useful tool for mechanistic interrogation of LuAd progression.


2004 ◽  
Vol 10 (8) ◽  
pp. 2742-2750 ◽  
Author(s):  
Julien Mazieres ◽  
Teresita Antonia ◽  
Ghislaine Daste ◽  
Carlos Muro-Cacho ◽  
Delphine Berchery ◽  
...  

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