Ophthalmology, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Xi'an, Shaanxi, 710068, China.
Xi'an Medical University, No.1 Xinwang Road, Xi'an, Shaanxi, 710021, China.
J Mol Neurosci. 2018 Feb;64(2):252-261. doi: 10.1007/s12031-017-1017-7. Epub 2017 Dec 20.
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.
最近的证据表明，Disheveled-Axin 结构域包含 1（DIXDC1）在各种癌症中失调。然而，DIXDC1 在视网膜母细胞瘤（RB）中的作用尚不清楚。在这项研究中，我们旨在研究 DIXDC1 在 RB 中的生物学功能及其表达受 microRNAs（miRNAs）调节的方式。我们发现 DIXDC1 在 RB 细胞系中的表达明显上调。通过小干扰 RNA（siRNA）沉默 DIXDC1 显著抑制了 RB 细胞系的增殖、侵袭和 Wnt 信号通路。有趣的是，DIXDC1 被鉴定为 miR-186 的靶基因。DIXDC1 的表达受 miR-186 的负调控，并且 DIXDC1 的表达与 RB 临床标本中 miR-186 的表达呈负相关。miR-186 的过表达抑制了 RB 细胞系的增殖、侵袭和 Wnt 信号通路。此外，DIXDC1 的过表达显著逆转了 miR-186 的抗肿瘤作用。总体而言，我们的研究结果表明 DIXDC1 在 RB 中作为潜在的癌基因发挥作用，miR-186 通过抑制 DIXDC1 抑制 RB 细胞系的增殖和侵袭。我们的研究表明，DIXDC1 和 miR-186 可能成为治疗 RB 的新的治疗靶点。
