Background: MicroRNAs (miRNAs) have been shown to contribute to the initiation and progression of human cancer, including retinoblastoma. However, expression levels and potential roles of miRNAs in retinoblastoma remain largely unknown. In this study, we aimed to identify dysregulated miRNAs and explore their functional roles in the development of retinoblastoma.
Material and Methods: First, miRNA expression profiling in retinoblastoma tissues was performed via microarray analysis. To evaluate the involvement of miR-214-3p in multi-drug resistance, gain-of-function experiments were employed in vitro and in vivo. Bioinformatics analysis, luciferase reporter assay, qRT-PCR and Western blot were used to investigate the underlying mechanisms.
Results: Here, we identified 57 up-regulated and 34 down-regulated miRNAs. Among them, miR-214-3p was the most significantly decreased. We found that miR-214-3p level was positively correlated with clinical outcome and chemotherapy response. Overexpression of miR-214-3p significantly sensitized retinoblastoma cells to multiple chemodrugs and promoted cell apoptosis in vitro and in vivo. Further investigations revealed that miR-214-3p directly regulated ABCB1 and XIAP expression through interacting with the 3’ untranslated regions (3’UTRs). Pearson correlation analysis showed that miR-214-3p expression in retinoblastoma tissues was negatively correlated with ABCB1 and XIAP expression. We also observed that overexpression of ABCB1 or XIAP partly reversed the chemoresistance inhibition-induced by miR-214-3p overexpression.
Conclusion: Our data demonstrate that miR-214-3p functions as a tumor suppressor to inhibit the chemoresistance in retinoblastoma, suggesting that miR-214-3p might be potential diagnostic and therapeutic targets for retinoblastoma treatment.
Keywords: retinoblastoma, miR-214-3p, chemoresistance, ABCB1, XIAP