Integrative Bioinformatic Approach for microRNA Interactome Networks in Human Papillomavirus-16 Infection

Objective: High-risk human papillomavirus (HPV), particularly HPV-16, is a major driver of carcinogenesis. Despite advances in understanding HPV-mediated oncogenesis, the role of microRNA (miRNA) interactome networks in HPV-16-driven tumorigenesis remains unclear. Using an integrative bioinformatic approach, this study identified key miRNAs, target genes, and transcription factors (TFs) involved in HPV-16-associated cancers. Methods: Human papillomavirus-16-associated miRNAs were retrieved from viRBase. microRNAs and their interactors were analyzed using The Cancer Genome Atlas and Genotype-tissue Expression datasets to investigate the expression patterns and potential roles in carcinogenesis. microRNA-messenger RNA (mRNA) interactions, TFs enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and GO terms analyses uncovered molecular networks disrupted by HPV-16. Receiver operating characteristic curve (ROC) and Kaplan-Meier analyses assessed the clinical significance of dysregulated miRNAs. Results: Eight miRNAs (hsa-miR-16-5p, hsa-miR-24-3p, hsa-miR-34a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-203a-3p, hsa-miR-205-5p, and hsa-miR-331-3p) were significantly dysregulated in HPV-16 infection and enriched in key KEGG pathways, highlighting involvement in cellular processes and regulatory mechanisms. Among these, hsa-miR-100-5p, hsa-miR-125b-5p, and hsa-miR-331-3p were the most significant in HPV-16-driven cancer types, with hsa-miR-125b-5p emerging as a key prognostic regulator. MAP3K13 and NR1H4 were identified as critical gene and TF candidates in HPV-16 carcinogenesis. Conclusion: This study provides novel insights into miRNA interactome networks in HPV-16-driven carcinogenesis, identifying biomarkers and therapeutic targets. Integrating translational bioinformatic insights with experimental validation paves the way for developing targeted diagnostic and therapeutic strategies and unravelling complex host-virus interactions, ultimately enhancing the management of HPV-associated cancers.