Tumor Biology

, Volume 36, Issue 3, pp 2041–2048

MiR-451 inhibits cell growth and invasion by targeting CXCL16 and is associated with prognosis of osteosarcoma patients

Research Article

DOI: 10.1007/s13277-014-2811-2

Cite this article as:
Zhang, F., Huang, W., Sheng, M. et al. Tumor Biol. (2015) 36: 2041. doi:10.1007/s13277-014-2811-2

Abstract

Recent studies have shown that microRNA-451 (miR-451) was significantly decreased in osteosarcoma tissues and was identified as a tumor suppressor in other types of human cancers. However, its clinical significance and molecular mechanisms in osteosarcoma are still not well understood. MiR-451 levels are evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in osteosarcoma cell lines and in 68 pairs of osteosarcoma and adjacent noncancerous tissues. Then, the associations of miR-451 expression with clinicopathological features of patients were determined. The effects of miR-451 in osteosarcoma cells were examined by MTT and Matrigel invasion assay. The functional target of miR-451 were determined by bioinformatics analysis and validated by luciferase reporter analyses and Western blot assay. Our results showed that the expression of miR-451 was significantly downregulated in osteosarcoma tissues compared with corresponding noncancerous tissues (P < 0.01). Particularly, statistical analysis of primary human osteosarcoma indicated that decreased expression of miR-451 was correlated with metastasis and recurrence. Moreover, the miR-451 force-expression suppressed cell proliferation and invasion in vitro. Based on bioinformatics analysis, we found that chemokine ligand 16 (CXCL16) was identified as a direct functional target of miR-451. Consistent with the effects of miR-451, silencing CXCL16 could phenocopy the effects of miR-451 on phenotypes of osteosarcoma cells. Furthermore, CXCL16 expression was upregulated in osteosarcoma tissues and inversely associated with miR-451 in human osteosarcoma tissues. Our data reveal a downregulated expression of miR-451 in osteosarcoma tissues, which is inversely associated with CXCL16 levels. These observations demonstrated that miR-451 may play an important role in tumor growth and metastasis in osteosarcoma.

Keywords

Osteosarcoma MiR-451 CXCL16 Cell proliferation Cell invasion 

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Fei Zhang
    • 1
  • Wei Huang
    • 3
  • Meixia Sheng
    • 4
  • Tielong Liu
    • 2
  1. 1.Department of OrthopedicsNingbo Development Zone Center HospitalNingboChina
  2. 2.Department of Orthopedics, Changzheng HospitalSecond Military Medical UniversityShanghaiChina
  3. 3.Department of Orthopedicsthe Sixth People’s Hospital of HangzhouHangzhouChina
  4. 4.Department of Respiratory MedicineHospital of LongsaiNingboChina

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