Bmi1 knockdown inhibits hepatocarcinogenesis.

ABSTRACT

Although Bmi1 is well established as one of the most commonly activated oncogenes, the precise role of Bmi1 during hepatocarcinogenesis remains unclear. In addition, Bmi1 provides a potential therapeutic target for the future treatment of hepatocellular carcinoma (HCC). In this study, the expression of Bmi1 in HCC tissues was evaluated by immunohistochemistry and western blot analysis. We found that Bmi1 was much more highly expressed in HCC tissue compared to normal liver tissue. The shRNA-mediated knockdown of Bmi1 was used to assess the effects of Bmi1 in hepatocarcinogenesis. Bmi1 downregulation reduced cell growth and tumorsphere formation in vitro. A cell cycle analysis using flow cytometry clarified that Bmi1 knockdown blocked the cell cycle transition from the G0/G1 to the S phase. Additionally, the Bmi1 knockdown led to reduced tumorigenicity in vivo. Furthermore, Bmi1 expression enhanced the sensitivity of HCC to the therapeutic agent, sorafenib. Taken together, the current results demonstrate that Bmi1 functions as a promoter in cell proliferation and hepatocarcinogenesis, providing a potential therapeutic target for the future treatment of HCC.