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Medical Oncology

, 31:972 | Cite as

MiR-34c inhibits osteosarcoma metastasis and chemoresistance

  • Meng Xu
  • Hua Jin
  • Cheng-Xiong XuEmail author
  • Wen-Zhi Bi
  • Yan WangEmail author
Original Paper

Abstract

Studies have shown that miR-34c is associated with metastasis and the chemoresponse of several cancers, but its role in osteosarcoma (OS) is unclear. Here, we investigated the role and mechanism of miR-34c in OS metastasis and chemoresponse. In this study, we found that the expression of miR-34c was significantly decreased in specimens from OS patients with a poor chemoresponse or metastasis compared to those with a good chemoresponse and no metastasis. The inhibition of miR-34c significantly stimulated OS cell invasion and chemoresistance in vitro. In contrast, restoring miR-34c significantly inhibited OS cell invasion and chemoresistance. Furthermore, we identified Notch1 and lymphoid enhancer-binding factor 1 (LEF1) as target genes of miR-34c in OS cells and demonstrated that Notch1 and LEF1 have a major role in the effects of miR-34c on OS cell chemosensitivity and metastasis. Taken together, our data indicate that miR-34c suppresses OS metastasis and chemoresistance by targeting Notch1 and LEF1. Restoring miR-34c may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy.

Keywords

MiR-34c Osteosarcoma Metastasis Chemoresistance 

Notes

Acknowledgments

This work was supported by the National High Technology Research and Development Program of China (2011AA030101); and the China International Medical Foundation (CIMF-F-H001-240).

Conflict of interest

The authors have no conflict of interest to declare.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of OrthopaedicsThe General Hospital of Chinese People’s Liberation ArmyBeijingChina
  2. 2.Department of Pharmaceutical Sciences, College of PharmacyUniversity of South FloridaTampaUSA
  3. 3.Departments of Molecular OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

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