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

Yue-Ming Ling, Jin-Yu Chen, Libin Guo, Chen-Yi Wang, Wen-Ting Tan, Qing Wen, Shu-Dong Zhang, Guo-Hong Deng, Yao Lin, Hang Fai Kwok

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Abstract

β-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 β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-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 β-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse β-defensin 1-associated gene signature. Furthermore, the downregulation of β-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated 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 β-defensin 1 plays an important role in protecting HCV progression and liver cancer development.

Original languageEnglish
Article number13404
Pages (from-to)1-14
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 17 Oct 2017

Keywords

  • Journal Article

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    Ling, Y-M., Chen, J-Y., Guo, L., Wang, C-Y., Tan, W-T., Wen, Q., Zhang, S-D., Deng, G-H., Lin, Y., & Kwok, H. F. (2017). β-defensin 1 expression in HCV infected liver/liver cancer an important role in protecting HCV progression and liver cancer development. Scientific Reports, 7(1), 1-14. [13404]. https://doi.org/10.1038/s41598-017-13332-0