BACKGROUND C-Type Lectin Domain Family 3 Member B (CLEC3B), is down-regulated in serum and tumor tissues in different cancers including hepatocellular carcinoma (HCC). However, the functions of CLEC3B in HCC remains elucidated. The aim of this study is to analyze the roles of CLEC3B in HCC. METHODS The expression of genes was evaluated by immunohistochemistry, western blot, real-time PCR, enzyme-linked immunosorbent assays, and analysis on TCGA-LIHC database and gene expression omnibus. Transmission electron microscopy and immunofluorescence were applied to detect CLEC3B in exosomes. The function of exosomal CLEC3B in tumor progression were performed in vivo and in vitro. RESULTS We determined that down-regulated CLEC3B in HCC indicated a poor prognosis. Exosomes derived from HCC with down-regulated CLEC3B promoted migration, invasion, epithelial-mesenchymal transition of both tumor cells and endothelial cells (ECs). Moreover, the downregulation CLEC3B in exosomes suppressed VEGF secretion in both HCC cells and ECs, and eventually inhibited angiogenesis. Mechanistically, CLEC3B-mediated VEGF expression in tumor cells and ECs depends on the activation of AMPK signal pathway. CONCLUSION This study demonstrates that CLEC3B acts as a novel independent prognostic factor, and CLEC3B in exosomes might be a potential therapeutic target for hepatocellular carcinoma.

中文翻译：

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肝细胞癌中外体CLEC3B的下调通过AMPK和VEGF信号促进转移和血管生成。

背景技术C型凝集素结构域家族3成员B（CLEC3B）在包括肝细胞癌（HCC）的不同癌症中的血清和肿瘤组织中被下调。但是，CLEC3B在肝癌中的功能仍然被阐明。这项研究的目的是分析CLEC3B在肝癌中的作用。方法通过免疫组织化学，western blot，实时荧光定量PCR，酶联免疫吸附试验，并在TCGA-LIHC数据库和基因表达综合分析中评估基因的表达。应用透射电镜和免疫荧光检测外泌体中的CLEC3B。体内和体外进行了外体CLEC3B在肿瘤进展中的功能。结果我们确定肝癌中CLEC3B的下调指示预后不良。从肝癌中衍生的外泌体与下调的CLEC3B一起促进了迁移，侵袭，肿瘤细胞和内皮细胞（EC）的上皮-间质转化。此外，外泌体中CLEC3B的下调抑制了HCC细胞和EC中的VEGF分泌，并最终抑制了血管生成。从机理上讲，CLEC3B介导的VEGF在肿瘤细胞和EC中的表达取决于AMPK信号通路的激活。结论这项研究表明，CLEC3B可作为一种新的独立预后因素，而外泌体中的CLEC3B可能是肝细胞癌的潜在治疗靶标。CLEC3B介导的VEGF在肿瘤细胞和EC中的表达取决于AMPK信号通路的激活。结论这项研究表明，CLEC3B可作为一种新的独立预后因素，而外泌体中的CLEC3B可能是肝细胞癌的潜在治疗靶标。CLEC3B介导的VEGF在肿瘤细胞和EC中的表达取决于AMPK信号通路的激活。结论这项研究表明，CLEC3B可作为一种新的独立预后因素，而外泌体中的CLEC3B可能是肝细胞癌的潜在治疗靶标。