β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development

beta-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that beta- defensin 1 was significantly reduced in HCVinfected liver specimens. Treatment with interferon and ribavirin upregulated beta-defensin-1, but not other beta-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated beta-defensin family expression in liver cancer in publicly available datasets and found that among all the beta-defensins tested, only beta-defensin 1 was significantly downregulated, suggesting beta-defensin 1 plays a crucial role in liver cancer development. Further analysis identified E-cadherin as the top positive correlated gene, while hepatocyte growth factor-regulated tyrosine kinase substrate as the top negative correlated gene. Expression of two proteoglycans were also positively correlated with that of beta-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse beta-defensin 1-associated gene signature. Furthermore, the downregulation of beta-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factorregulated tyrosine kinase substrate, were further confirmed in liver cancer and adjacent normal tissue collected from in-house Chinese liver cancer patients. Together, our results suggest beta-defensin 1 plays an important role in protecting HCV progression and liver cancer development.