Exploring the Shared miRNA-mRNA Signature Network Between Helicobacter pylori Infection and Gastric Cancer: A...

Gastric cancer (GC) is the fifth most prevalent cancer worldwide, with Helicobacter pylori (H. pylori) infection as the leading cause. MicroRNAs (miRNAs), critical post-transcriptional regulators of gene expression, play pivotal roles in both H. pylori infection and GC pathogenesis. However, not all the dysregulated miRNAs exert a downstream effect on mRNAs, steering the pathologies. Utilising GEO datasets and literature curation, we compiled a comprehensive list of human differentially expressed (hDE) miRNAs in H. pylori-infected cell lines (HP-hDEmiRs) and GC tissues (GC-hDEmiRs). The identified targets of hDEmiRs from publicly available databases were compared with hDEmRNAs retrieved from GEO in each pathology to build a miRNA-mRNA network exhibiting inverse expression patterns, and the resultant miRNAs were considered as 'Functional hDEmiRs'. Subsequently, 24 upregulated and 10 downregulated functional HP-hDEmiRs with 57 and 18 targets and 38 upregulated and 7 downregulated functional GC-hDEmiRs with 230 and 20 targets were identified, respectively. The miRNA-mRNA network of functional GC-hDEmiRs was validated using GC-hDEmRNAs from TCGA and a shared subset of functional hDEmiRs in H. pylori infection and GC was identified. This includes the upregulated hsa-miR-98-5p, hsa-miR-21-5p, hsa-let-7c-5p, hsa-let-7f-5p, hsa-let-7i-5p, hsa-miR-15a-5p, hsa-miR-181b-5p, hsa-miR-25-3p and the downregulated hsa-miR-204-5p, that could have a combinatorial effect in H. pylori infection to GC progression. Moreover, along with the TCGA-validated hydroxyacyl-CoA dehydrogenase (HADH), the epithelial splicing regulatory protein-2 (ESRP2) and dihydrolipoamide branched chain transacylase E2 (DBT) were downregulated in both conditions, possibly attributed to the effect of functional hDEmiRs targeting them. Our findings offer potential candidates for miRNA-directed therapeutics in these pathologies.