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.

Cite this article as: Doğan B. Integrative bioinformatic approach for miRNA interactome networks in HPV16 infection. Eurasian J Med. 2025, 57(3), 0817, doi: 10.5152/eurasianjmed.2025.25817.