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.

MicroRNA-21 Down-regulates Rb1 Expression by Targeting PDCD4 in Retinoblastoma.

Retinoblastoma (RB) is a children's ocular cancer caused by mutated retinoblastoma 1 (Rb1) gene on both alleles. Rb1 and other related genes could be regulated by microRNAs (miRNA) via complementarily pairing with their target sites. MicroRNA-21 (miR-21) possesses the oncogenic potential to target several tumor suppressor genes, including PDCD4, and regulates tumor progression and metastasis. However, the mechanism of how miR-21 regulates PDCD4 is poorly understood in RB. We investigated the expression of miRNAs in RB cell lines and identified that miR-21 is one of the most deregulated miRNAs in RB. Using qRT-PCR, we verified the expression level of several miRNAs identified by independent microarray assays, and analyzed miRNA expression patterns in three RB cell lines, including Weri-Rb1, Y79 and RB355. We found that miR-19b, -21, -26a, -195 and -222 were highly expressed in all three cell lines, suggesting their potential role in RB tumorigenesis. Using the TargetScan program, we identified a list of potential target genes of these miRNAs, of which PDCD4 is one the targets of miR-21. In this study, we focused on the regulatory mechanism of miR-21 on PDCD4 in RB. We demonstrated an inverse correlation between miR-21 and PDCD4 expression in Weri-Rb1 and Y79 cells. These data suggest that miR-21 down-regulates Rb1 by targeting PDCD4 tumor suppressor. Therefore, miR-21 could serve as a therapeutic target for retinoblastoma.