Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Key Laboratory of Proteomics, Dalian Medical University, Dalian, China.
J Cell Biochem. 2018 Sep;119(9):7738-7746. doi: 10.1002/jcb.27125. Epub 2018 Jun 15.
Nogo-B receptor (NgBR) is a type I receptor with a single transmembrane domain and specifically binds to ligand Nogo-B. A previous study demonstrated that NgBR was highly expressed in human breast invasive ductal carcinoma and promoted epithelial-mesenchymal transition in breast tumor cells. Our recent work found that NgBR expression was associated with a poor prognosis in human patients with hepatocellular carcinoma (HCC). Here, we elucidate that the increased expression of NgBR contributes toward the increased cell growth of human HCC cells both in vitro and in vivo. Cell viability and clonogenic survival analysis results demonstrated that knockdown of NgBR inhibits the cell growth in human HCC cells, which correlates with a reduction in the phosphorylation of Akt levels. Furthermore, overexpression of NgBR by the cotransfected pIRES-NgBR plasmid together with NgBR siRNA in human HCC cells can rescue impaired phosphorylation of Akt levels in NgBR knockdown human HCC cells. In addition, cell viability analyses showed that NgBR overexpression can rescue the cell growth inhibition presented in human HCC NgBR knockdown cells. Taken together, our results suggest that NgBR potentially acts as an oncogene in HCC by increasing Akt activity. Thus, NgBR may represent a new potential diagnostic and therapeutic target for the treatment of HCC.
神经生长抑制因子-B 受体（NgBR）是一种具有单一跨膜结构域的 I 型受体，特异性结合配体神经生长抑制因子-B。先前的研究表明，NgBR 在人乳腺浸润性导管癌中高表达，并促进乳腺肿瘤细胞的上皮-间充质转化。我们最近的工作发现，NgBR 的表达与人类肝细胞癌（HCC）患者的预后不良有关。在这里，我们阐明了 NgBR 的表达增加有助于人 HCC 细胞在体外和体内的细胞生长增加。细胞活力和集落形成存活分析结果表明，NgBR 的敲低抑制了人 HCC 细胞的细胞生长，这与 Akt 水平的磷酸化减少相关。此外，在人 HCC 细胞中转染 pIRES-NgBR 质粒与 NgBR siRNA 共转染可使 NgBR 敲低的 HCC 细胞中 Akt 水平磷酸化受损得到恢复。此外，细胞活力分析表明，NgBR 的过表达可以挽救人 HCC NgBR 敲低细胞中出现的细胞生长抑制。总之，我们的结果表明，NgBR 通过增加 Akt 活性可能在 HCC 中充当致癌基因。因此，NgBR 可能代表 HCC 治疗的新的潜在诊断和治疗靶点。
