Novel role of semaphorin 3A in the growth and progression of hepatocellular carcinoma

Abstract

Semaphorin3A(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 80HCC 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 invitro. 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, enolase2 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, enolase2 and EpCAM expression to promote HCC progression and is a potential therapeutic target for HCC.