Open Access

The microRNA‑708‑5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma

  • Authors:
    • Tianyu Feng
    • Zhongkai Zhu
    • Yaqian Jin
    • Hao Wang
    • Xiaohan Mao
    • Dan Liu
    • Yiling Li
    • Lixia Lu
    • Guowei Zuo
  • View Affiliations

  • Published online on: December 31, 2019     https://doi.org/10.3892/or.2019.7452
  • Pages: 491-502
  • Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA‑708‑5p (miR‑708‑5p) and epithelial‑​to‑mesenchymal transition (EMT) have been widely identified to contribute to the pathogenesis and progression of multiple cancers. However, the connection between miR‑708‑5p and EMT has not been sufficiently clarified. Therefore, our research aimed to investigate the impact of miR‑708‑5p on EMT and the metastasis of osteosarcoma (OS). We first analyzed the differentially expressed microRNAs (DEmiRNAs) from the GSE70367 dataset. We found that the expression of miR‑708‑5p was lower in OS cells. Overexpression of miR‑708‑5p was able to impair the migration and invasion of OS cells. Moreover, miR‑708‑5p inhibited EMT of OS cells MG63 and SaOS‑2, wherein E‑cadherin was increased, and N‑cadherin, vimentin, and Snail were decreased. Semaphorin 4C (SEMA4C), mitogen‑activated protein kinase kinase kinase 3 (MAP3K3), and zinc finger E‑box‑binding homeobox 1 (ZEB1) were predicted as target genes of miR‑708‑5p by bioinformatics method. Only ZEB1, one of the EMT‑inducing transcription factors, was validated as the direct target gene of miR‑708‑5p in OS cells through dual‑luciferase reporter assay and Western blot analysis. Knockdown of ZEB1 was found to inhibit the metastasis of MG63 and SaOS‑2 cells, whereas ZEB1 over­expression promoted their metastasis. In summary, miR‑708‑5p impaired the metastasis and EMT of OS, which was found to be mediated by inhibition of ZEB1.
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February 2020
Volume 43 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Feng, T., Zhu, Z., Jin, Y., Wang, H., Mao, X., Liu, D. ... Zuo, G. (2020). The microRNA‑708‑5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma. Oncology Reports, 43, 491-502. https://doi.org/10.3892/or.2019.7452
MLA
Feng, T., Zhu, Z., Jin, Y., Wang, H., Mao, X., Liu, D., Li, Y., Lu, L., Zuo, G."The microRNA‑708‑5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma". Oncology Reports 43.2 (2020): 491-502.
Chicago
Feng, T., Zhu, Z., Jin, Y., Wang, H., Mao, X., Liu, D., Li, Y., Lu, L., Zuo, G."The microRNA‑708‑5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma". Oncology Reports 43, no. 2 (2020): 491-502. https://doi.org/10.3892/or.2019.7452