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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
Whole-Transcriptome Profiling of Canine and Human in Vitro Models Exposed to a G-Quadruplex Binding Small Molecule
Eleonora Zorzan1, Ramy Elgendy1,2, Mery Giantin1
1Department of Comparative Biomedicine and Food Science, University of Padua, Legnaro, Padua, Italy.
Abstract:
G-quadruplexes (G4) are secondary nucleic acid structures that have been associated with genomic instability and cancer progression. When present in the promoter of some oncogenes, G4 structures can affect gene regulation and, hence, represent a possible therapeutic target. In this study, RNA-Seq was used to explore the effect of a G4-binding anthraquinone derivative, named AQ1, on the whole-transcriptome profiles of two common cell models for the study of KIT pathways; the human mast cell leukemia (HMC1.2) and the canine mast cell tumor (C2). The highest non-cytotoxic dose of AQ1 (2 µM) resulted in 5441 and 1201 differentially expressed genes in the HMC1.2 and C2 cells, respectively. In both cell lines, major pathways such as cell cycle progression, KIT- and MYC-related pathways were negatively enriched in the AQ1-treated group, while other pathways such as p53, apoptosis and hypoxia-related were positively enriched. These findings suggest that AQ1 treatment induces a similar functional response in the human and canine cell models, and provide news insights into using dogs as a reliable translational model for studying G4-binding compounds.
Insights
This study explores how AQ1, a G-quadruplex (G4) binder, affects gene expression in human and canine cancer cells. AQ1 treatment impacts key cancer pathways, suggesting dogs may be a useful model for G4-targeting cancer therapies.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- G-quadruplexes (G4) are secondary nucleic acid structures implicated in genomic instability and cancer.
- G4 structures in oncogene promoters can influence gene regulation, presenting therapeutic targets.
Purpose of the Study:
- To investigate the whole-transcriptome effects of the G4-binding compound AQ1.
- To compare AQ1's impact on human (HMC1.2) and canine (C2) mast cell models.
Main Methods:
- RNA-sequencing (RNA-Seq) was employed to analyze gene expression profiles.
- Two cell lines, HMC1.2 (human) and C2 (canine), were treated with the highest non-cytotoxic dose of AQ1 (2 µM).
Main Results:
- AQ1 treatment resulted in 5441 differentially expressed genes in HMC1.2 cells and 1201 in C2 cells.
- Key pathways like cell cycle, KIT, and MYC were negatively enriched, while p53, apoptosis, and hypoxia pathways were positively enriched in both cell lines.
- AQ1 induced similar functional responses in both human and canine models.
Conclusions:
- AQ1 treatment elicits conserved transcriptomic responses across human and canine mast cell models.
- These findings support the utility of canine models for studying G4-binding compounds in cancer research.
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