microRNA‑485 inhibits the malignant behaviors of retinoblastoma by directly targeting Wnt3a

  • Authors:
    • Xueman Lyu
    • Ling Wang
    • Jia Lu
    • Hong Zhang
    • Lina Wang
  • View Affiliations

  • Published online on: March 13, 2019     https://doi.org/10.3892/or.2019.7061
  • Pages: 3137-3147
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Abstract

Deregulation of microRNAs (miRNAs) has been widely reported in retinoblastoma (RB), and the aberrantly expressed miRNAs may serve as crucial epigenetic regulators in the occurrence and development of RB. Therefore, the identification of dysregulated miRNAs in RB may be useful for the development of effective targets for the therapy patients with this disease. miRNA (miR)‑485‑5p (miR‑485) is deregulated in multiple human cancer types and serves crucial roles in their progression and development. However, the expression pattern of miR‑485 and its role in RB have not been well investigated. In the present study, expression levels of miR‑485 in RB tissues and cell lines were measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The effects of miR‑485 overexpression on RB cell proliferation, apoptosis, migration and invasion were examined using Cell Counting Kit‑8 assay, flow cytometric analysis and in vitro migration and invasion assays, respectively. Xenograft tumor formation assay was utilized to determine the influence of miR‑485 on RB tumor growth in vivo. The mechanism responsible for the tumor‑suppressing roles of miR‑485 in RB progression was determined through a series of experiments, including bioinformatics prediction, luciferase reporter assay, RT‑qPCR, western blot analysis and rescue experiments. Herein, a marked downregulation of miR‑485 expression in human RB tissues and cell lines was observed. miR‑485 overexpression suppressed RB cell proliferation, induced cell apoptosis, attenuated cell migration and cell invasion in vitro, and restrained the growth of RB cells in vivo. Additionally, Wnt3a was revealed to be a direct target gene of miR‑485 in RB cells. Wnt3a was upregulated in human RB tissues, and its upregulation was inversely associated with miR‑485. Furthermore, the tumor suppressive roles of Wnt3a silencing were similar to those of miR‑485 overexpression in RB cells. In addition, restoration of Wnt3a expression partially reversed the tumor suppressor action of miR‑485 in RB cells. However, miR‑485 upregulation directly targeted Wnt3a to inhibit activation of the Wnt/β‑catenin signaling pathway in RB cells both in vitro and in vivo. Notably, these results demonstrated that the tumor‑suppressive roles of miR‑485 were at least partially mediated by Wnt3a in RB cells. Therefore, miR‑485 is a potential therapeutic target for treating patients with RB.

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May 2019
Volume 41 Issue 5

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APA
Lyu, X., Wang, L., Lu, J., Zhang, H., & Wang, L. (2019). microRNA‑485 inhibits the malignant behaviors of retinoblastoma by directly targeting Wnt3a. Oncology Reports, 41, 3137-3147. https://doi.org/10.3892/or.2019.7061
MLA
Lyu, X., Wang, L., Lu, J., Zhang, H., Wang, L."microRNA‑485 inhibits the malignant behaviors of retinoblastoma by directly targeting Wnt3a". Oncology Reports 41.5 (2019): 3137-3147.
Chicago
Lyu, X., Wang, L., Lu, J., Zhang, H., Wang, L."microRNA‑485 inhibits the malignant behaviors of retinoblastoma by directly targeting Wnt3a". Oncology Reports 41, no. 5 (2019): 3137-3147. https://doi.org/10.3892/or.2019.7061