Tumor Biology

, Volume 36, Issue 5, pp 3799–3806 | Cite as

Demethylation-mediated miR-129-5p up-regulation inhibits malignant phenotype of osteogenic osteosarcoma by targeting Homo sapiens valosin-containing protein (VCP)

  • Xin Hua Long
  • Yun Fei Zhou
  • Ai Fen Peng
  • Zhi Hong Zhang
  • Xuan Yin Chen
  • Wen Zhao Chen
  • Jia Ming Liu
  • Shan Hu Huang
  • Zhi Li Liu
Research Article

Abstract

Previous studies demonstrated that increased Homo sapiens valosin-containing protein (VCP) may be involved in osteosarcoma (OS) metastasis. However, the underlying mechanism of VCP over-expression in OS remains unknown. In the present study, we found a significantly negative correlation between miR-129-5p and VCP protein expression in OS tissues with pulmonary metastasis (Spearman's rho, rs = −0.948). Bioinformatical prediction, Luciferase reporter assay, Western blot, and RT-PCR assays performed on OS cells indicated that VCP is a target of miR-129-5p. In addition, three CPG islands in the region of miR-129-5p promoter were detected by bioinformatical prediction, and significantly higher expression of miR-129-5p and lower methylation level of miR-129-2 gene in OS cells treated with 5-Aza-2′-deoxycytidine (a potent DNA demethylating agent) than in those untreated cells were observed. Furthermore, lower migratory and invasive ability was found in cells with elevated miR-129-5p than in those with decreased miR-129-5p. These findings indicated that increased miR-129-5p may be mediated by demethylation and inhibit OS cell migration and invasion by targeting VCP in OS, and targeting miR-129-5p/VCP signaling pathway may serve as a therapeutic strategy for OS management, although further studies will be necessary.

Keywords

Demethylation miR-129-5p Osteosarcoma Malignant phenotype Valosin-containing protein 

Notes

Acknowledgments

The present study was supported by grants from the National Natural Science Foundation of China (No. 81360399) and the Natural Science Foundation of Jiangxi Province (No. 2012ZBAB205016).

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xin Hua Long
    • 1
  • Yun Fei Zhou
    • 1
  • Ai Fen Peng
    • 2
  • Zhi Hong Zhang
    • 1
  • Xuan Yin Chen
    • 1
  • Wen Zhao Chen
    • 1
  • Jia Ming Liu
    • 1
  • Shan Hu Huang
    • 1
  • Zhi Li Liu
    • 1
  1. 1.Department of OrthopedicsThe First Affiliated Hospital of Nanchang UniversityNanchangPeople’s Republic of China
  2. 2.Jiangxi University of Traditional Chinese MedicineNanchangPeople’s Republic of China

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