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Tumor Biology

, Volume 37, Issue 11, pp 14939–14947 | Cite as

The tumor suppressor miR-124 inhibits cell proliferation and invasion by targeting B7-H3 in osteosarcoma

  • Ling Wang
  • Fu-biao Kang
  • Nan Sun
  • Juan Wang
  • Wei Chen
  • Dong Li
  • Bao-en ShanEmail author
Original Article

Abstract

Our previous studies have shown that the expression level of B7 homolog 3 (B7-H3) was correlated with clinical staging and prognosis of osteosarcoma (OS) patients, and its silencing inhibited the proliferation and invasion of OS cells in vitro. However, its overexpression mechanism behind was far from elucidated. On the basis of bioinformatics and the preliminary screening data, we hypothesized that miR-124 might play an important role in OS development and as a lead candidate for modulating B7-H3 expression. In this study, we found that miR-124 was downregulated significantly in OS tumor tissue, compared to normal adjacent tissues (NATs). Lower miR-124 expression levels were associated with advanced Ennecking stage, lower tumor differentiation, and common pulmonary metastasis. The 5-year overall survival rate in the miR-124 upregulated group was 61.5 %, while with low miR-124 expression, only 11.8 % survived. Further studies in vitro showed that B7-H3 was a direct target of miR-124. Overexpression of miR-124 decreased B7-H3 mRNA and protein level and inhibited B7-H3 3′-UTR reporter activity. Treatment of OS cells with miR-124 mimics induced the inhibition of cell growth and invasion in vitro, which could be abrogated by transfected by B7-H3 expression vector. Our findings highlight the potential application of miR-124 as a novel onco-miRNA in OS, and its oncogenic effects are mediated chiefly through downregulation of B7-H3, thus suggesting a model for identifying miR-124 that can be exploited to improve the therapeutic potential efficacy of mAb targeting to B7-H3.

Keywords

Osteosarcoma miR-124 B7-H3 Proliferation Invasion 

Notes

Acknowledgments

This program was financially supported by the National Natural Science Foundation of China (81402228), Hebei Natural Science Foundation (H2015206216), HeBei Province Medical Foundation (ZL20140334), and HeBei Province Education Foundation (QN2014049).

Compliance with ethical standards

Conflicts of interest

None

Authors’ contributions

The conception and design were initiated by FBK and LW; NS, JW, and WC performed clinical data acquisition and drafted the manuscript; DL contributed in the statistical analysis; BES directed the study and helped revised the paper. All authors read and approved the final manuscript.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Ling Wang
    • 1
    • 2
  • Fu-biao Kang
    • 3
  • Nan Sun
    • 4
  • Juan Wang
    • 2
  • Wei Chen
    • 2
  • Dong Li
    • 3
  • Bao-en Shan
    • 1
    Email author
  1. 1.Cancer Research Institutethe Fourth Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China
  2. 2.Department of OrthopedicsThe Third Hospital of Hebei Medical UniversityShijiazhuangChina
  3. 3.Department of Liver DiseasesBethune International Peace HospitalShijiazhuangPeople’s Republic of China
  4. 4.Blood transfusion divisionthe Fourth Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China

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