The regulatory role of exosomal CagA and microRNAs derived from H. pylori -related gastric cancer cells on signaling pathways related to cancer development: a bioinformatics aspect

Exosomes are small vesicles outside the membrane, which are secreted by healthy, cancerous, and bacterial infected cells. These worthy vesicles carry shared information between adjacent cells and cause cell-cell communication. Bacteria can also secrete vesicles similar to exosomes called outer membrane vesicles (OMVs). The OMVs, also called quasi-exosomes due to its similarity to exosomes, are bacterial extracellular membrane vesicles that are secreted to enhance the pathogenicity of the bacteria. The continued secretion of exosome by cells and quasi-exosome by bacteria in gastric cancer played a vital role in cancer progression to metastasis and acute cancer state. In gastric cancer associated with Helicobacter pylori infection, both cancerous and immune cells secretion are involved. Exosomes and quasi-exosomes interact with each other to overcome cancer or worsen it. Cancer cells, through the involvement of T lymphocytes and macrophages, make these cells to secrete. Exosomes stimulate the immune system and improve gastric cancer. Exosomes containing CagA, miR155, MET, and GGT factors play an important role in gastric cancer. The regulatory role of some of these factors such as microRNAs and CagA are evaluated by enrichment analysis. KEGG pathway analysis illustrated the most significant pathway of upregulated gene in gastric cancer patient with inflammation history of H. pylori. Functional annotation analysis of H. pylori-related gastric sample highlighted the cluster of genes which regulated signal transduction and cellular respond to stimulus mechanism. Also, the protein-protein interaction (PPI) network of upregulated genes manifest CXCL8, CDC42, and BDKRB2 genes as a core network. Regarding the augmentation role of candidate genes in metastasis, migration, and angiogenesis in gastric cancer and also their regulatory role in pathogenesis and expansion of H. pylori, these genes offer the therapeutic opportunity against H. pylori and gastric cancer parallelly. Our final analysis was based on microRNAs related database underline mir-499, mir-208a-3p, and mir-208b which are the most downregulated microRNAs in H. pylori-related gastric cancer and could serve as an anti-cancer therapeutic agent.