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MicroRNA-21 Targets PDCD4 expression in Retinoblastoma Open Access

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Background: The retinoblastoma is a children's ocular cancer caused by mutated retinoblastoma gene (Rb1) on both alleles. MiRNAs regulate their target gene expression by complementarily pairing with its target sites. MiR-21 possesses oncogenic ability in targeting several tumor suppressor genes, and regulates tumor progression and metastasis. PDCD4 (Programmed Cell Death 4) is one of its target genes. However, the mechanism of the regulation of PDCD4 by miR-21 is poorly understood in retinoblastoma. The aim of this study was focused on the differential expression of miRNAs in retinoblastoma cell lines, and on elucidating the functional role of miR-21 in regulating PDCD4 target gene. Results: Analysis of previously published miRNA microarray data by others resulted in a list of potentially important miRNAs in retinoblastoma. Using TaqMan qRT-PCR, the expressions of miRNAs were detected in three retinoblastoma cell lines, Weri-Rb1, Y-79 and RB355. MiR-19b, -21, -26a, -195 and -222 were found to be significantly expressed in all three cell lines and lists of probable target genes were presented. An inverse correlation of miR-21 and PDCD4 protein levels were observed in Weri-Rb1 and Y-79 cells. Moreover, PDCD4 regulation by miR-21 was examined in gain-of -function and loss-of -function analysis. Up-regulated miR-21 diminished PDCD4 protein expression in pre-miR-21-transfected Weri-Rb1 cells, while inhibition of miR-21 in RB355 cells increased PDCD4 protein level.Conclusions: We have shown the differential expression of miR-19b, -21, -26a, -195 and -222 among the retinoblastoma cell lines, suggesting their role in retinoblastoma tumorigenesis. MiR-21 as an oncomiR, targets PDCD4 and regulates its expression in retinoblastoma, which may have a therapeutic potential in retinoblastoma treatment.

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