Homeobox B5 suppression attenuates proliferation and elevates apoptosis in hepatoma cell lines through ERK/MDM2 signalling.

Abstract

Homeobox B5 (HOXB5), a member of the HOX gene family, is an important gene in tumourigenesis. However, its role in hepatocellular carcinoma (HCC) cell proliferation and apoptosis remains unclear. In this study, we investigated the role and regulation mechanism of HOXB5 in HCC cell lines Hep3B and LM6. The data indicated high expression of HOXB5 in HCC tissues and cell lines. In HCC cells, inhibition of HOXB5 by transfection with HOXB5 siRNA significantly constrained cell viability, and Bcl-2 levels, and it increased cell apoptosis, cytochrome c levels, BAX levels, and caspase-3 activity. On the contrary, HOXB5 overexpression increased proliferation and Bcl-2 levels but inhibited BAX levels and caspase-3 activity in these cells. HOXB5 downregulation attenuated activation of extracellular signal-regulated kinase (ERK) and expression of the murine double minute 2 (MDM2) oncogene. Incubation with the ERK activator, phorbol 12-myristate 13-acetate (40μmol/L), for 12hours reversed the effects of HOXB5 inhibition on MDM2 expression, cell proliferation, and apoptosis in HCC cells. Overall, this study demonstrated that HOXB5 inhibition regulated MDM2 expression by controlling ERK activation and that it modulated proliferation and apoptosis in HCC cells.