Viral modulation of angiogenesis through microRNA networks: Implications for cancer biology, biomarkers, and therapy.

Abstract

Angiogenesis is essential for development, tissue repair, and vascular homeostasis, whereas dysregulated neovascularization contributes to chronic inflammation, ischemic injury, and cancer progression. Viral infections can reshape vascular programs through endothelial signaling, immune responses, metabolic stress, and noncoding RNA networks. MicroRNAs (miRNAs), including host-derived and virus-encoded species, regulate endothelial proliferation, migration, permeability, and vessel formation. This review examines how major viral families, including Herpesviridae, Hepadnaviridae, Papillomaviridae, and emerging pathogens, modulate vascular biology through miRNA-centered mechanisms. Rather than cataloguing individual virus-miRNA interactions, we provide a cross-viral framework integrating virus-encoded miRNAs, virus-regulated host miRNAs, extracellular RNA transfer, and their convergence on hypoxic, inflammatory, metabolic, and angiogenic pathways. We distinguish persistent tumor-supportive angiogenesis from vasculogenic mimicry, inflammatory vascular remodeling, endothelial injury, and anti-angiogenic responses. We further evaluate evidence strength, experimental limitations, biomarker potential, and therapeutic opportunities involving antagomiRs, miRNA mimics, engineered extracellular-vesicle delivery, and pathway-directed interventions. This framework positions miRNAs as context-dependent regulatory nodes whose translational value will depend on causal target validation, tissue-specific delivery, and clinically robust patient stratification.