Suppression of Disheveled-Axin Domain Containing 1 (DIXDC1) by MicroRNA-186 Inhibits the Proliferation and Invasion of Retinoblastoma Cells.

ABSTRACT

Recent evidence shows that Disheveled-Axin domain containing 1 (DIXDC1) is dysregulated in various cancers. However, the role of DIXDC1 in retinoblastoma (RB) remains unclear. In this study, we aimed to investigate the biological function of DIDXDC1 in RB and the way in which its expression is regulated by microRNAs (miRNAs). We found that DIXDC1 expression was significantly upregulated in RB cell lines. The silencing of DIXDC1 by small interfering RNA (siRNA) significantly inhibited the proliferation, invasion, and Wnt signaling in RB cell lines. Interestingly, DIXDC1 was identified as a target gene of miR-186. The expression of DIXDC1 was negatively regulated by miR-186, and DIXDC1 expression was inversely correlated with miR-186 expression in RB clinical specimens. Overexpression of miR-186 inhibited the proliferation, invasion, and Wnt signaling in RB cell lines. Moreover, overexpression of DIXDC1 markedly reversed the antitumor effect of miR-186. Overall, our results reveal that DIXDC1 functions as a potential oncogene in RB, and inhibiting DIXDC1 by miR-186 suppresses the proliferation and invasion of RB cell lines. Our study suggests that DIXDC1 and miR-186 may serve as novel therapeutic targets for the treatment of RB.