Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to Nitric Oxide

• Main Authors: Arnatchai Maiuthed, Ornjira Prakhongcheep, Pithi Chanvorachote
• Other Authors: Chulalongkorn University
• Format: Article
• Published: 2020
• Subjects: Biochemistry, Genetics and Molecular Biology
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/57704
• Institution: Mahidol University

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. 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.