Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis

Abstract

Entamoeba histolytica (E. histolytica) is an anaerobic parasite that causes Amoebiasis in the intestine or extraintestinal, with immunology, genetics, and environmental variables all playing a part in the disease's development, but its molecular mechanism is unknown. One of the primary obstacles in understanding the etiology of Amoebiasis will be identifying the genetics profiling that controls the Amoebiasis network. By examining the gene expression profile of Amoebiasis and comparing it with healthy controls, we could identify differentially expressed genes (DEGs). DEGs were used to build the Amoebiasis protein interaction network and calculated its network topological properties. We discovered nine key hub genes (KHGs): JUN, PTGS2, FCGR3A, MNDA, CYBB, EGR1, CCL2, TLR8, and LRRK2 genes. The genes JUN and EGR1 were transcriptional factors (TFs) and up-regulated, others down-regulated. hsa-miR-155-5p, hsa-miR-101-3p, hsa-miR-124-3p, hsa-miR-26b-5p, and hsa-miR-16-5p are also among the essential miRNAs that have been demonstrated to be targeted by KHGs. These KHGs were primarily enriched in the IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, and Toll-like receptor signaling pathway. miRNAs were grouped in various pathways, focusing on the TGF-β signaling pathway, human immunodeficiency virus 1 infection, insulin signaling pathway, signaling pathways regulating pluripotency of stem cells, etc. Amoebiasis KHGs (JUN, PTGS2, CCL2, and MNDA) and their associated miRNAs are the primary targets for therapeutic methods and possible biomarkers. Furthermore, we identified drugs for genes JUN, PTGS2, FCGR3A, CCL2, and LRRK2. KHGs, on the other hand, required experimental validation to prove their efficacy.

Keywords: Amoebiasis infection; Differentially expressed genes (DEGs); Gene-interaction network.

Figure 1. Schematic diagram of the workflow

Detailed workflow of methods implemented in Amoebiasis infection-associated PPI network study.

Figure 2. Volcano plot of the down-regulated and up-regulated DEGs

The volcano plot shows the down-regulated and up-regulated DEGs of Amoebiasis infected and healthy cases. The x-axis represents the log₂(FC) and the y-axis represents −log₁₀ (P-values).

Figure 3. PPI network of DEG

Up- and down-regulated genes are represented as yellow and blue colors, respectively.

Figure 4. GO analysis of down-regulated DEGs

The GO of DEGs. The x-axis represents the gene ratio. The color of the dots represents the −log₁₀(P) and the size of the dots represents the gene count. (A) Biological process and (B) molecular function.

Figure 5. GO analysis of down-regulated DEGs

(A) Cellular component and (B) KEGG pathways

Figure 6. GO analysis of up-regulated DEG sets

The x-axis represents the gene ratio. The color of the dots represents the −log₁₀(P-value), and the size of the dots represents the gene count. (A) Biological process and (B) molecular function.

Figure 7. GO analysis of up-regulated DEG sets

The x-axis represents the gene ratio. The color of the dots represents the −log₁₀(P-value) and the size of the dots represents the gene count. (A) Cellular component and (B) KEGG pathways.

Figure 8. KEGG pathways analysis for KHGs

The color of the dots represents the −log₁₀(P-value), the size of the dots represents the gene count, and the x-axis represents the gene ratio.

Figure 9. Visualization of miRNAs-gene regulatory network and KEGG pathway analysis

(A) A miRNA–gene regulatory network contains the KHGs (JUN, PTGS2, CCL2, and MNDA). Green ellipse shape and yellow diamonds represent genes and miRNAs, respectively. (B) The dot plot represents the KEGG pathway analysis of miRNAs. The x-axis represents the miRNAs, and the y-axis represents the KEGG pathways. The color of the dots represents the adjusted P-value (FDR), and the size of the dots represents the gene ratio.

Figure 10. MIENTURNET network analysis of hub genes and differentially expressed miRNAs

Dot plot of functional enrichments analysis of target miRNAs resulting from enrichment analysis. The x-axis represents the miRNAs, and the y-axis represents reactome and disease ontology analysis.