miR-101, downregulated in retinoblastoma, functions as a tumor suppressor in human retinoblastoma cells by targeting EZH2

Accumulating evidence indicates that microRNAs are involved in multiple processes in cancer development and progression, and several miRNAs have emerged as candidate components of oncogene or tumor-suppressor networks in retinoblastoma. miR-101 has been identified as a tumor suppressor in several types of human cancer. However, the specific function of miR-101 in retinoblastoma remains unclear. In the present study, we found that the expression of miR-101 in retinoblastoma tissues was much lower than that in the normal controls. In addition, downregulation of miR-101 more frequently occurred in retinoblastoma specimens with adverse clinicopathological and histopathological features. In addition, miR-101 inhibited cell viability and progression in retinoblastoma cells by promoting cell apoptosis and arresting the cell cycle. Finally, we found that miR-101 directly inhibited EZH2 expression by targeting its 3'-UTR, and EZH2 was upregulated and inversely correlated with miR-101 expression in the retinoblastoma tissues. Thus, for the first time, we provide convincing evidence that downregulation of miR-101 is associated with tumor aggressiveness in retinoblastoma and inhibits cell growth and proliferation of retinoblastoma cells by targeting EZH2. In conclusion, all the evidence supports the tumor-suppressor role of miR-101 in human retinoblastoma.