Upregulated expression of polycomb protein Ring1 contributes to poor prognosis and accelerated proliferation in human hepatocellular carcinoma.

Abstract

Ring finger protein 1 (Ring1) have recently been reported to be closely related to aggressive tumor features in multiple cancer types, including prostate cancer, non-small-cell lung cancer, and bladder cancer. However, the role of Ring1 in human hepatocarcinogenesis remains unclear. In this study, we aimed at investigating the latent role of Ring1 in hepatocellular carcinoma (HCC) development. The expression of Ring1 was evaluated using Western blot analysis in 8 paired fresh HCC tissues and immunohistochemistry on 98 paraffin-embedded sections from 2005 to 2008. Moreover, RNA interference, CCK-8, colony formation, and flow-cytometry analyses were performed to investigate the role of Ring1 in the regulation of HCC cell proliferation. Compared with adjacent normal tissues, the level of Ring1 was significantly increased in HCC specimens. High expression of Ring1 was associated with histological grade (P = 0.011) and tumor size (P = 0.004), and Ring1 expression was positively related with the proliferation marker Ki-67 (P < 0.001). Moreover, knocking down Ring1 induced growth impairment and G1/S cell cycle arrest in HCC cells. Kaplan-Meier survival curves showed that high expression of Ring1 indicated poor prognosis of HCC (P = 0.03). On the basis of these results, we proposed that the expression of Ring1 protein may be a novel indicator of HCC prognosis.