β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development.
β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development.
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β-防御素 1 在 HCV 感染的肝癌/肝癌中的表达：在保护 HCV 进展和肝癌发展中发挥重要作用
DOI：
10.1038/s41598-017-13332-0
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发表时间：
2017-10-17
影响因子：
4.6
通讯作者：
Kwok HF
中科院分区：
文献类型：
--
作者：
Ling YM;Chen JY;Guo L;Wang CY;Tan WT;Wen Q;Zhang SD;Deng GH;Lin Y;Kwok HF
β-防御素家族在宿主防御病毒感染中发挥作用，但在HCV感染中的作用尚不清楚。在本研究中，我们证明了β-防御素1在hcv感染的肝脏标本中显著降低。干扰素和利巴韦林治疗上调β-防御素-1，但其他β-防御素测试没有上调，上调的程度和持续时间与治疗反应相关。我们在公开的数据集中研究了β-防御素家族在肝癌中的表达，发现在所有测试的β-防御素中，只有β-防御素1显著下调，这表明β-防御素1在肝癌的发展中起着至关重要的作用。进一步分析发现E-cadherin是最高的正相关基因，而肝细胞生长因子调节的酪氨酸激酶底物是最高的负相关基因。两种蛋白聚糖的表达也与β-防御素1的表达呈正相关。我们还确定了小分子作为逆转β-防御素1相关基因特征的潜在治疗剂。此外，从中国肝癌患者体内收集的肝癌及邻近正常组织中进一步证实了β-防御素1和E-cadherin的下调，肝细胞生长因子调节的酪氨酸激酶底物的上调。总之，我们的研究结果表明β-防御素1在保护HCV进展和肝癌发展中起重要作用。
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.
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