Subtype-Specific miRNA Expression Profiling in HPV-Associated Cervical Cancer: Insights into Oncogenic Pathways and Biomarker Potential

Abstract Cervical cancer driven by high-risk human papillomavirus (HPV) infections, remains a global health concern. Despite advances in understanding HPV-mediated carcinogenesis, the role of microRNAs (miRNAs) in subtype-specific oncogenesis remains underexplored. This study aims to profile miRNA expression patterns in cervical cancer cell lines emphasizing subtype-specific dysregulation and its implications for diagnostic and therapeutic strategies. Four cervical cancer cell lines representing HPV16, HPV18, HPV68, and HPV-negative were profiled for miRNAs expression using NanoString nCounter™ Human V3 miRNA Panel. Differentially expressed miRNAs were identified based on fold-change ≥2.0, p-value <0.05, and false discovery rate (FDR) < 0.3. Predicted target gene of miRNAs were identified from TarBase, TargetScan, and microT-CDS. Further enrichment analysis and protein-protein interaction (PPI) network were performed using DIANA-miRPath and STRING software respectively. Subtype-specific clustering revealed 18 distinct miRNA signatures unique to different HPV subtypes with miR-205-5p and miR-125b-5p were the most up-regulated and down-regulated, respectively. Bioinformatic analyses, identified PI3K-Akt signaling as a key cancer-associated pathway implicated in tumor proliferation and survival. These findings advance understanding of miRNA-driven molecular mechanisms in HPV subtype-specific cervical carcinogenesis. miR-205-5p and miR-125b-5p are potential biomarkers and therapeutic targets toward precision medicine approaches in cervical cancer management. Further validation is warranted to integrate these findings into clinical practice.