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

Feng,Tianyu; Zhu,Zhongkai; Jin,Yaqian; Wang,Hao; Mao,Xiaohan; Liu,Dan; Li,Yiling; Lu,Lixia; Zuo,Guowei

doi:10.3892/or.2019.7452

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
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Affiliations: Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, P.R. China
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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