Network-based integration of hsa-miR-150-5p reveals key regulatory roles in HIV-HCV coinfection and HCV-associated hepatocellular carcinoma.

HIV-HCV coinfection markedly accelerates liver fibrosis and hepatocellular carcinoma (HCC), yet the molecular regulators driving this progression remain elusive. MicroRNAs (miRNAs) orchestrate host-virus interactions, but their roles in coinfection are poorly defined. Here, we applied an integrative multi-omics strategy to profile plasma miRNAs from cohorts of HIV, HCV, HIV-HCV coinfection, and healthy controls, followed by TaqMan qRT-PCR validation. Cross-referencing with HCV-HCC transcriptomes (GSE6764, GSE14323, GSE62232) and experimentally confirmed targets from miRTarBase enabled high-confidence network mapping. Among dysregulated miRNAs, hsa-miR-150-5p and hsa-miR-141-3p emerged with striking HCV-specific expression patterns, absent in HIV monoinfection. hsa-miR-150-5p was strongly upregulated, with targets significantly repressed in HCV-HCC. Enrichment analysis revealed its regulatory footprint across chromosome dynamics, mitotic control, and oncogenic signalling (Notch, HIF-1, JAK-STAT, p53). Protein-protein interaction expansion identified 202 first-degree interactors, with KRAS, BAP1, and HMGB1 as high-centrality hubs linking miR-150-5p to core oncogenic and immune pathways. KEGG analysis of the extended network revealed dominant impacts on organismal systems, environmental signalling, and genetic information processing, all of which are pivotal to liver tumorigenesis. In contrast, hsa-miR-141-3p showed limited integration and minimal pathway association. These findings suggest that hsa-miR-150-5p is a key regulator in HCV-associated liver disease, with upregulation observed in both HCV and HIV-HCV coinfection groups, potentially influencing transcriptional and network-level regulation. This systems-level framework highlights miR-150-5p as a potential biomarker for HCV and HIV-HCV associated liver pathology, providing a basis for future studies toward precision interventions in viral coinfection-mediated oncogenesis.