Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to Nitric Oxide.
Biomarkers, Tumor
/ analysis
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Epigenesis, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Kruppel-Like Factor 4
Lung Neoplasms
/ drug therapy
Neoplastic Stem Cells
/ drug effects
Nitric Oxide
/ pharmacology
Transcription Factors
/ genetics
Tumor Cells, Cultured
Nitric oxide
bioinformatics
epigenetic modifications
lung cancer
microarrays
transcription factors
Journal
Cancer genomics & proteomics
ISSN: 1790-6245
Titre abrégé: Cancer Genomics Proteomics
Pays: Greece
ID NLM: 101188791
Informations de publication
Date de publication:
Historique:
received:
13
02
2020
revised:
11
03
2020
accepted:
13
03
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
12
2
2021
Statut:
ppublish
Résumé
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. We used bioinformatics and pharmacological experiments to elucidate the potential regulation and underlying mechanisms of NO in non-small a lung cancer cell model. 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. Through this comprehensive approach, the present study illustrated the scheme of how NO affects molecular events in lung cancer cells.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
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
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
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
CONCLUSIONS
Through this comprehensive approach, the present study illustrated the scheme of how NO affects molecular events in lung cancer cells.
Identifiants
pubmed: 32576585
pii: 17/4/401
doi: 10.21873/cgp.20199
pmc: PMC7367602
doi:
Substances chimiques
Biomarkers, Tumor
0
KLF4 protein, human
0
Kruppel-Like Factor 4
0
Transcription Factors
0
Nitric Oxide
31C4KY9ESH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
401-415Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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