Bioinformatic Analysis of the Effect of Silver Nanoparticles on Colorectal Cancer Cell Line
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Fernando Martínez-Esquivias1, Melva Gutiérrez-Angulo2, Julieta Saraí Becerra-Ruiz1
1Instituto de Investigación en Biociencias, Centro Universitario de Los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, Jalisco, Mexico.
Abstract:
Colorectal cancer (CRC) is the most diagnosed cancer with the highest mortality rate each year globally. Although there are treatments for CRC, the development of resistance to therapies decreases the success of treatments. In vitro studies using the Caco-2 cell line have revealed the anticancer properties of silver nanoparticles (AgNPs) as a possible treatment for this disease. This study considered four researches that evaluated the proteomic profiles of cells of the Caco-2 line exposed to AgNPs. We performed a bioinformatics analysis to predict protein-protein interaction, hub genes, Gene Ontology (molecular function, biological process, and cellular components), KEGG pathways, analysis of expression, and immune cell infiltration. For these analyses, the STRING, DAVID, UALCAN, GEPIA2, and TISIDB databases were used. The results in Gene Ontology show that AgNPs cause a deregulation of genes related to cell-cell adhesion, the cytoplasm, the centriole, and carbon metabolism. Hub genes were identified, including GADPH, ENO1, EEF2, and ATP5A1, which showed differential expression in patients with adenocarcinoma of the colon and rectum. Additionally, the expression of the hub genes and immune cells was correlated. It was found that ATP5A1 and ENO1 were positively correlated with the infiltration of CD4+ T lymphocytes in colon adenocarcinoma and a negative correlation between GADPH and PDIA3 with the infiltration of NK cells and CD4+ T lymphocytes in rectal adenocarcinoma, respectively. In conclusion, the administration of AgNPs causes an alteration of biological processes, cellular components, metabolic pathways, deregulation of hub genes, and the activity of immune cells leading to a potential anticancer effect.
Insights
Silver nanoparticles (AgNPs) show anticancer properties against colorectal cancer (CRC) by altering cellular processes and gene expression. This study reveals AgNPs
Area of Science:
- Nanomedicine and Cancer Therapeutics
- Bioinformatics and Computational Biology
- Molecular Oncology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide.
- Therapeutic resistance significantly limits the efficacy of current CRC treatments.
- Silver nanoparticles (AgNPs) have demonstrated potential anticancer properties in vitro using the Caco-2 cell line.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the anticancer effects of AgNPs on colorectal cancer cells.
- To perform a comprehensive bioinformatics analysis of proteomic data from AgNP-exposed Caco-2 cells.
- To identify key genes, pathways, and immune cell interactions modulated by AgNPs.
Main Methods:
- Bioinformatics analysis of four existing studies on proteomic profiles of Caco-2 cells treated with AgNPs.
- Utilized STRING, DAVID, UALCAN, GEPIA2, and TISIDB databases for analysis.
- Evaluated protein-protein interactions, hub genes, Gene Ontology terms, KEGG pathways, gene expression, and immune cell infiltration.
Main Results:
- AgNPs induced deregulation in genes associated with cell-cell adhesion, cytoplasm, centriole, and carbon metabolism.
- Identified hub genes (GADPH, ENO1, EEF2, ATP5A1) with differential expression in colorectal adenocarcinoma.
- Correlated hub gene expression with immune cell infiltration, noting positive correlations for ATP5A1 and ENO1 with CD4+ T cells, and negative correlations for GADPH and PDIA3 with NK cells and CD4+ T cells, respectively.
Conclusions:
- AgNP administration alters critical biological processes, cellular components, and metabolic pathways in colorectal cancer cells.
- AgNPs modulate the expression of key regulatory genes (hub genes) implicated in colorectal cancer.
- AgNPs influence immune cell activity, suggesting a potential multifaceted anticancer effect.
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