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Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to
Arnatchai Maiuthed1, Ornjira Prakhongcheep2,3, Pithi Chanvorachote4,3
1Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Background/Aim:
Nitric oxide (NO) is recognized as an important biological mediator that exerts several human physiological functions. As its nature is an aqueous soluble gas that can diffuse through cells and tissues, NO can affect cell signaling, the phenotype of cancer and modify surrounding cells. The variety of effects of NO on cancer cell biology has convinced researchers to determine the defined mechanisms of these effects and how to control this mediator for a better understanding as well as for therapeutic gain.
Materials And Methods:
We used bioinformatics and pharmacological experiments to elucidate the potential regulation and underlying mechanisms of NO in non-small a lung cancer cell model.
Results:
Using microarrays, we identified a total of 151 NO-regulated genes (80 up-regulated genes, 71 down-regulated genes) with a strong statistically significant difference compared to untreated controls. Among these, the genes activated by a factor of more than five times were: DCBLD2, MGC24975, RAB40AL, PER3, RCN1, MRPL51, PTTG1, KLF5, NFIX. On the other hand, the expression of RBMS2, PDP2, RBAK, ORMDL2, GRPEL2, ZNF514, MTHFD2, POLR2D, RCBTB1, JOSD1, RPS27, GPR4 genes were significantly decreased by a factor of more than five times. Bioinformatics further revealed that NO exposure of lung cancer cells resulted in a change in transcription factors (TFs) and epigenetic modifications (histone modification and miRNA). Interestingly, NO treatment was shown to potentiate cancer stem cell-related genes and transcription factors Oct4, Klf4, and Myc.
Conclusion:
Through this comprehensive approach, the present study illustrated the scheme of how NO affects molecular events in lung cancer cells.
Insights
Nitric oxide (NO) regulates 151 genes in lung cancer cells, affecting transcription factors and epigenetic modifications. This study reveals NO
Area of Science:
- Molecular biology
- Cancer research
- Bioinformatics
Background:
- Nitric oxide (NO) is a key biological mediator influencing cell signaling and cancer phenotypes.
- Understanding NO's diverse effects on cancer cells is crucial for therapeutic strategies.
Purpose of the Study:
- To elucidate the regulatory mechanisms and molecular pathways of nitric oxide (NO) in non-small cell lung cancer.
- To identify genes and transcription factors modulated by NO in lung cancer.
Main Methods:
- Bioinformatics analysis of gene expression data.
- Pharmacological experiments in a non-small cell lung cancer model.
- Microarray analysis to identify NO-regulated genes.
Main Results:
- Identified 151 differentially expressed genes (80 up, 71 down) regulated by NO.
- Observed significant changes in transcription factors and epigenetic modifications (histone modification, miRNA) upon NO exposure.
- NO treatment potentiated cancer stem cell-related genes and transcription factors (Oct4, Klf4, Myc).
Conclusions:
- Nitric oxide significantly impacts molecular events in lung cancer cells.
- The study provides a comprehensive overview of NO's molecular effects in lung cancer.
- Findings contribute to understanding NO's role and potential therapeutic applications in lung cancer.
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