Targeting overexpressed oncogenes in esophageal cancer through miRNA-mediated gene silencing: Insights from binding...

Esophageal cancer (ESCA) ranks among the most lethal malignancies worldwide, with late-stage diagnosis, poor prognosis, and limited treatment options contributing to its high mortality. MicroRNAs (miRNAs), short non-coding RNAs with gene-silencing functions, have emerged as crucial regulators in cancer biology and hold promise as diagnostic and therapeutic tools. This study investigates miRNA-mRNA interactions in ESCA using a comprehensive in silico approach to uncover potential regulatory nodes that may underlie tumor progression. Fourteen overexpressed genes in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) were selected. TargetScanHuman and miRDB were used to detect miRNAs with high-confidence 8mer seed matches (score ≥90). The majority of genes exhibited multi-miRNA targeting with clustered or overlapping seed regions, indicative of cooperative or redundant repression mechanisms. Several miRNAs demonstrated highly stable interactions, with favorable MFE and ΔG values, reinforcing their silencing potential. GC/GC3 enrichment further supported duplex stability. GO analysis revealed that the target genes are predominantly involved in transcriptional regulation, apoptosis inhibition, immune response modulation, and cell signaling-pathways central to cancer pathogenesis. TCGA-based validation showed that only a subset of predicted interactions is functionally relevant, with hsa-miR-30d-5p exhibiting a significant inverse correlation with CHST2. These findings highlight the importance of integrating predictive and expression data to identify biologically meaningful miRNA-mRNA interactions in esophageal cancer.