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VEGF-mediated suppression of cell proliferation and invasion by miR-410 in osteosarcoma

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Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. The aberrant expression of miRNA has become a major focus in cancer research. This study aimed to investigate the importance of miR-410 in the diagnosis and therapy of osteosarcoma (OS). Western blot analysis showed that the expression of VEGF was higher in Saos-2 and MG-63 cells than that in three other OS cell lines. We also found that miR-410 was lowly expressed and inversely correlated with VEGF expression in OS specimens. Over-expression of miR-410 had a greater repression on VEGF expression than other candidate VEGF-targeting miRNAs. Luciferase reporter assay demonstrated that miR-410 directly decreased VEGF expression by targeting its 3′-untranslated region. Further investigation demonstrated the regulation of miR-410 in OS cells via VEGF. In vitro MTT assay, Transwell, and flow cytometry showed that transfection of the miR-410 expression plasmid inhibited cell proliferation and contributed to apoptosis in OS cells. Moreover, restoration of VEGF reversed the effect of miR-410 on OS cells, and upregulated the expression of phosphorylated AKT. Finally, overexpression of miR-410 also showed a negative effect on tumor growth in vivo. Our findings suggest a cooperative relationship between miR-410 and VEGF in OS cell regulation. This information may help researchers to better understand miRNA regulation in cancer and provide a rationale for developing miRNA-based strategies for OS treatment.

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Acknowledgments

This project was supported by National Natural Science Foundation of China (81201281), Natural Science Foundation of Hebei Province of China (C2012401037, H2013209180), and the project of Science and Technology from Government of Tangshan City of Hebei Province (12140209A-4).

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The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Orthopedics, Affiliated Hospital, Logistics University of Chinese People’s Armed Police Forces, No. 220 Chenglin Road, Hedong district, Tianjin, 300162, China

    Dong Zhao, Peng Jia & Wenliang Wang

  2. School of Basic Medical Sciences, Hebei United University, No. 57 Jianshe Road, Tangshan City, 063000, Hebei Province, China

    Guangling Zhang

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  1. Dong Zhao
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  2. Peng Jia
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  3. Wenliang Wang
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  4. Guangling Zhang
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Correspondence to Dong Zhao or Guangling Zhang.

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Zhao, D., Jia, P., Wang, W. et al. VEGF-mediated suppression of cell proliferation and invasion by miR-410 in osteosarcoma. Mol Cell Biochem 400, 87–95 (2015). https://doi.org/10.1007/s11010-014-2265-2

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  • DOI: https://doi.org/10.1007/s11010-014-2265-2

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