Novel role of semaphorin 3A in the growth and progression of hepatocellular carcinoma
Novel role of semaphorin 3A in the growth and progression of hepatocellular carcinoma
复制标题
信号蛋白3A在肝细胞癌生长和进展中的新作用
DOI：
10.3892/or.2017.5616
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发表时间：
2017-06-01
期刊：
影响因子：
4.2
通讯作者：
Dai, Zhi
中科院分区：
文献类型：
--
作者：
Li, Xuedong;Chen, Qing;Dai, Zhi
脑信号蛋白3A（Semaphorin 3A，SEMA 3A）是脑信号蛋白家族的成员之一，在肿瘤细胞的生物学行为和肿瘤相关巨噬细胞的调节中发挥重要作用。然而，SEMA 3A在肝细胞癌（HCC）中的作用仍然没有很好地建立。在本研究中，我们研究了SEMA 3A在80个肝癌组织和细胞系的表达水平，采用RT-qPCR，免疫印迹和免疫组化。表达谱分析显示，SEMA 3A在人HCC患者中显著过表达，并且与HCC细胞的转移潜能正相关。将慢病毒转染入PLC/PRF/5和HCCLM 3细胞中以稳定上调和下调HCC细胞中SEMA 3A的表达。细胞计数试剂盒-8（CCK-8）、伤口愈合和侵袭试验显示，SEMA 3A促进体外HCC细胞的增殖和迁移。蛋白质组分析仪抗体微阵列分析显示，SEMA 3A在HCC细胞中的过表达诱导凝溶胶样帽蛋白（CapG）、半乳糖凝集素-3、烯醇化酶2和上皮细胞粘附分子（EpCAM）的表达水平显著增加。此外，HCC细胞中SEMA 3A的上调促进了HCC小鼠模型中的肿瘤生长和进展。这些结果表明，SEMA 3A增强CapG、半乳糖凝集素-3、烯醇化酶2和EpCAM表达以促进HCC进展，并且是HCC的潜在治疗靶标。
Semaphorin 3A (SEMA3A), a secretory protein, is a founding member of the semaphorin family and functions in both the biological behavior of tumor cells and the modulation of tumor-associated macrophages. However, the role of SEMA3A in hepatocellular carcinoma (HCC) is still not well established. In the present study, we investigated the expression levels of SEMA3A in 80 HCC tissues and cell lines, using RT-qPCR, western blotting and immunohistochemistry. Expression profile analysis revealed that SEMA3A was significantly overexpressed in human HCC patients and positively correlated with the metastatic potential of HCC cells. Lentiviral transfection into PLC/PRF/5 and HCCLM3 cells was performed to stably upregulate and downregulate the expression of SEMA3A in HCC cells. Cell Counting Kit-8 (CCK-8), wound-healing and invasion assays revealed that SEMA3A promoted the proliferation and migration of HCC cells in vitro. Proteome profiler antibody microarray analysis revealed that overexpression of SEMA3A in HCC cells induced a significant increase in the expression levels of gelsolin-like capping protein (CapG), galectin-3, enolase 2 and epithelial cell adhesion molecule (EpCAM). Furthermore, the upregulation of SEMA3A in HCC cells promoted tumor growth and progression in an HCC mouse model. These results indicate that SEMA3A enhances CapG, galectin-3, enolase 2 and EpCAM expression to promote HCC progression and is a potential therapeutic target for HCC.