Rho
GDP dissociation inhibitor (GDI) beta, (
RhoGDI2), has been identified as a proto-oncogene that is upregulated in human
cancers, but the role of
RhoGDI2 in
hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the
RhoGDI2 expression level in HCC tissues and the function of
RhoGDI2 in HCC cell growth and
metastasis. We examined the
RhoGDI2 mRNA expression level in 64 sets of HCC tissue and their adjacent nontumor tissue counterparts using quantitative real-time polymerase chain reaction. In vitro proliferation and invasion assays were conducted to determine the effect of
RhoGDI2 on the ability of HCC cells to proliferate and invade, respectively. Western blot analysis was conducted to examine expression levels of RhoGDI2p-AKT, MMP-2, and MMP-9 in HCC cells.
RhoGDI2 mRNA was significantly overexpressed in the HCC specimens compared with the nonneoplastic liver specimens, and the
RhoGDI2 mRNA and
protein levels were higher in the HCC cell lines, especially the highly metastatic cell lines 97L and 97H. To further investigate the role that
RhoGDI2 plays in HCC, we overexpressed
RhoGDI2 using a lentivirus-mediated overexpression technique in two HCC cell lines (Huh7 and 7721) that endogenously express a low level of
RhoGDI2. Stable cells overexpressing
RhoGDI2 demonstrated a significant increase in cell proliferation and invasion. Furthermore, our additional findings indicated that RhoGDI2-mediated cellular invasion requires the PI3K/Akt signaling-dependent expression of
matrix metalloproteinases (
MMPs). Our findings suggest that
RhoGDI2 plays an important role in HCC growth and invasion and should be considered a novel HCC therapeutic target candidate.