Profiling gene expression and network analysis in human U937 cells in response to Solenopsin, a constituent of fire ant venom
The toxic effects of insect venom range from slight allergy to anaphylactic reactions and may even lead to death in humans. Despite its toxic nature, studies have shown that venom components of insects are of great therapeutic value (Ratclifee et al., 2011). Solenopsin, the alkaloidal content of the fire ant (Solenopsis invicta) venom inhibits PI3K signaling pathway and nitric oxide synthases (Arbiser et al., 2007, Yi et al., 2003). This implies the toxic effects of solenopsin is exhibited by altering cell signaling pathways and thus resulting in changes at gene expression level. Toxicity of the insect venoms can be harnessed and applied to its analogous counter parts relevant to human diseases like combating cancer cells and pathogenic microbials. A high-throughput analysis at this conjecture will help to analyze the changes at genes expression levels. The study aims to identify the solenopsin induced alteration in gene expression pattern within human U937 cell line; data for which is publicly available [Gene Expression Omnibus (GEO) accession id: GSE13102]. Significant genes were extracted with differential expression (fold change ≤ or ≥1.41 and p-value < 0.05; student's t-test). Out of 19,200 probes, a total of 433 genes were differentially regulated, of which 240 and 193 were upregulated and downregulated respectively. 126 of upregulated genes were associated with GO term: phosphoproteins; most of which are involved in metabolism. In the upregulated list, genes related to spliceosome complex are highly enriched in KEGG pathways. Protein interaction network analysis of downregulated genes revealed crosstalks between AKT/PIP3K, TGF-β and Wnt signaling pathways .Our results suggested that solenopsin inhibits AKT/PIP3K and TGF-β signaling pathways efficiently. Inhibition of TGF- β signaling by solenospin has not been identified/reported earlier. Integrating the results of this study with previous related studies, further research is demanded to enhance the therapeutic efficacy of solenopsin.
References:
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