scholarly journals Bioinformatic Analysis of Circadian Expression of Oncogenes and Tumor Suppressor Genes

2017 ◽  
Vol 11 ◽  
pp. 117793221774699
Author(s):  
Abbas Salavaty ◽  
Niloufar Mohammadi ◽  
Mozhdeh Shahmoradi ◽  
Maryam Naderi Soorki
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Expression Patterns ◽  
Bioinformatic Analysis ◽  
Gene Library ◽  
Statistical Software ◽  
Suppressor Genes ◽  
Circadian Genes ◽  
Circadian Expression ◽  
And Function

Background: Circadian rhythms are physiological and behavioral cycles with a period of approximately 24 hours that control various functions including gene expression. Circadian disruption is associated with a variety of diseases, especially cancer. Although some of the oncogenes and tumor suppressor genes (TSGs) are known as clock-controlled genes (CCGs), the analysis and annotation of circadian expression of most human oncogenes and TSGs are still lacking. This study aims to investigate the circadian expression of a list of human oncogenes and TSGs. Methods: A bioinformatic analysis was conducted on a gene library comprising 120 genes to investigate the circadian expression of human oncogenes and TSGs. To achieve this purpose, the genotranscriptomic data were retrieved from COSMIC and analyzed by R statistical software. Furthermore, the acquired data were analyzed at the transcriptomic and proteomic levels using several publicly available databases. Also, the significance of all analyses was confirmed statistically. Results: Altogether, our results indicated that 7 human oncogenes/TSGs may be expressed and function in a circadian manner. These oncogenes/TSGs showed a circadian expression pattern at CircaDB database and associated with at least one of the circadian genes/CCGs based on both genotranscriptomic and correlation analyses. Conclusions: Although 4 of 7 finally outputted genes have been previously reported to be clock controlled, heretofore there is no report about the circadian expression of 3 other genes. Considering the importance of oncogenes/TSGs in the initiation and progression of cancer, further studies are suggested for the identification of exact circadian expression patterns of these 3 human oncogenes/TSGs.

scholarly journals Circadian Expression of Clock- and Tumor Suppressor Genes in Human Oral Mucosa

2010 ◽  
Vol 26 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Derek Zieker ◽  
Isabel Jenne ◽  
Ingmar Koenigsrainer ◽  
Marty Zdichavsky ◽  
Kay Nieselt ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Oral Mucosa ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Circadian Expression

scholarly journals Easy or Not—The Advances of EZH2 in Regulating T Cell Development, Differentiation, and Activation in Antitumor Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaqi Huang ◽  
Jie Zhang ◽  
Zhengyang Guo ◽  
Chen Li ◽  
Zhen Tan ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Cell Fate ◽  
Tumor Suppressor Genes ◽  
T Cell Development ◽  
Suppressor Cells ◽  
Cell Development ◽  
Suppressor Genes ◽  
Polycomb Repressive Complex 2 ◽  
And Function

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2), which regulates downstream gene expression by trimethylation of lysine 27 in histone H3 (H3K27me3). EZH2 mutations or overexpressions are associated with many types of cancer. As inhibition of EZH2 activity could upregulate the expression of tumor suppressor genes, EZH2 has recently become an interesting therapeutic target for cancer therapy. Moreover, accumulating evidence has shown that EZH2 may contribute to the regulation of immune cells, especially T cells. EZH2 regulates T cell development, differentiation, and function, suggesting that EZH2 also regulates immune homeostasis in addition to tumor suppressor genes. Moreover, EZH2 can regulate T cell fate by targeting non-T cell factors such as metabolism, cytokines, and myeloid-derived suppressor cells. The role of EZH2 in this process has not been fully addressed. This review discusses up-to-date research on EZH2-mediated regulation of immunological function and the progress of immunological therapeutic strategies based on this regulation.

scholarly journals TMOD-18. TARGETING THE PI3K/AKT PATHWAY IN MYCN AMPLIFIED HIGH GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii231-ii232
Author(s):  
Katharine Halligan ◽  
Ann-Catherine Stanton ◽  
Matthew Halbert ◽  
Brian Golbourn ◽  
Stephen Mack ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Suppressor ◽  
Mouse Model ◽  
Protein Expression ◽  
Neural Stem Cells ◽  
Tumor Suppressor Genes ◽  
Akt Pathway ◽  
High Grade ◽  
Suppressor Genes ◽  
High Grade Gliomas

Abstract Pediatric glioblastoma (pGBM) are incurable brain tumors with overall poor prognosis and response to treatments due to molecular and epigenetic heterogeneity. In particular, the MYCN subtype of pGBM are a highly aggressive form of GBM with a dismal median survival of only 14 months. Furthermore, this subtype is enriched with loss of the tumor suppressor genes TP53 and PTEN, leading to aberrantly active PI3K-AKT signaling pathway and DNA-checkpoint abnormalities. Here, we report the generation of a novel syngeneic mouse model that recapitulates the features of the MYCN subtype of pGBM. We isolated Sox2-Cre neural stem cells from C57BL/6 mice and transduced inverted retroviral-cassettes of the murine Mycn oncogene simultaneously with shRNA targeting tumor suppressor genes p53 and Pten. Retroviral-cassettes are flanked by tandem LoxP sites arranged so that Cre recombinase expression inverts the cassettes in frame allowing for MYCN protein expression and loss of the P53/PTEN proteins. Transgene activation is accompanied with selectable cell surface markers and fluorescent tags enabling for fluorescent activated cell sorting (FACS) of the desired cell populations. Neural stem cells with MYCN protein expression and concurrent silencing of P53 and PTEN protein (NPP cells) result in significantly increased proliferation and activation of PI3K-AKT pathway as compared to control neural stem cells and have. Injection of NPP cells into the forebrain of immune competent C57BL/6 mice result in the formation of invasive high-grade gliomas with a lethal phenotype at ~50 days post injection. Using several next generation brain penetrant small molecule inhibitors of the PI3K-AKT pathway, we show inhibition of tumorigenesis in vitro. Moreover, we have identified several novel mechanisms of PI3KAKT treatment resistance and are currently identifying therapies that may overcome this resistance through RNA seq analysis. In summary, well defined genetic drivers of GBM can lead to informed mouse model generation to test promising therapies.

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