268 INHIBITORY EFFECT OF INCREASED GLUCOSYLCERAMIDE ON HEPATOCARCINOGENESIS IN KNOCKOUT MICE

Background and Objective: It has been reported that microribonucleic acid (miR)-101was down-regulated in some malignant tumors.Ectopic expression of miR-101 significantly inhibits cellular proliferation, migration and invasion of tumor cells by targeting polycomb group protein enhancer of zeste homolog 2 (EZH2).However, the specific role of miR-101 in human hepatocellular carcinoma (HCC) remains unclear.The aim of this study was to investigate the expression of miR-101 and EZH2 in HCC.Methods: miR-101and EZH2 expressions were evaluated in tumor and adjacent non-tumor liver tissues from 12 patients with HCC undergoing liver resection by the use of miRNA microarray.In addition, their expressions were assessed by real-time quantitative RT-PCR (qRT-PCR) analyses in six human hepatoma cell lines (HepG2, Hep3B, Huh7, PLC/PRF5, SNU-182 and HepaRG).The relationships between miR-101, EZH2 expressions and patient outcome were evaluated.Results: A significant down-regulation of miR-101 was observed in 83.3% of HCC tissues and in all of the six HCC cell lines (compared to human hepatocytes).In contrast, EZH2 expression was significantly increased in 91.7% of HCC samples and in all six cell lines.Moreover, decreased expression of miR-101 and increased expression of EZH2 in tumor tissue of patients were significantly associated with poor prognosis. Conclusions:The putative tumor suppressor miR-101 may negatively regulate its target EZH2 in HCC, and decreased expression of miR-101 may contribute to tumor progression by functional deregulation of EZH2 activity in HCC.