Dysregulation of FURIN and Other Proprotein Convertase Genes in the Progression from HPV Infection to Cancer

Productive infections of oncogenic human papillomaviruses (HPVs) are closely linked to the differentiation of host epithelial cells, a process that the virus manipulates to create conditions favorable to produce virion progeny. This viral interference involves altering the expression of numerous host genes. Among these, proprotein convertases (PCs) have emerged as potential oncogenes due to their central role in cellular functions. Using RT-qPCR, aberrant PC gene expression was detected across the progression from early HPV infection stages to cancer. These findings demonstrated a progressive disruption of normal PC expression profiles, with FURIN consistently downregulated and other PCs upregulated, transitioning from the episomal stage to neoplastic and carcinoma phenotypes. This pattern of dysregulation was distinct from the broader trends observed in a variety of cancer types through bioinformatic analysis of publicly available transcriptomic datasets, where FURIN expression was predominantly upregulated compared to other PCs. Further bioinformatic investigations revealed a correlation between PC gene expression and cancer phenotype diversity, suggesting a potential link between the loss of normal PC gene expression patterns and the progression of HPV infections toward malignancy.