肝细胞癌
癌症研究
车站3
癌变
MMP2型
免疫组织化学
信号转导
磷酸化
单克隆抗体
基因剔除小鼠
癌症
医学
生物
抗体
病理
内科学
免疫学
转移
受体
细胞生物学
作者
Fengjie Wan,Hui Li,Shiping Huang,Junming Sun,Jiafu Li,Yasi Li,Lichao Yang,Min He
标识
DOI:10.1016/j.cellsig.2023.110809
摘要
Abnormal expression of Vasorin (VASN) is related to many types of cancer, but the signaling pathway and mechanism of how VASN contributes to the carcinogenesis of hepatocellular carcinoma (HCC) are poorly understood. Here, we found that VASN was up-regulated in serum/serum exosome and tissues of HCC patients. The expression of VASN in serum improve the detection rate of HCC in alpha-fetoprotein-negative HCC patients. Immunohistochemistry revealed that VASN was highly expressed in HCC tissues and associated with different stages of HCC. Noticeably, when serum VASN combined with α-fetoprotein, the area under the curve (AUC), sensitivity, and specificity of HCC patients compared with healthy patients reached 0.918 (95% CI: 0.869-0.967, P < 0.001), 90.91%, and 90.20%, respectively. VASN knockout HCC cells were obtained by CRISPR/Cas9 and a VASN-specific monoclonal antibody was prepared by hybridoma technology. Knockout of VASN or the addition of VASN-specific monoclonal antibody suppressed the proliferation and migration of HCC. Mechanistically, VASN promote the proliferation and migration of HCC by regulating the phosphorylation of STAT3 and the expression of downstream genes CCND1 and MMP2. In conclusion, our findings suggest that VASN plays a crucial role in the activation of STAT3 signaling pathway in HCC, which is a promising target for the diagnosis and therapy of HCC.
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