Tumor Biology

, Volume 36, Issue 3, pp 2041–2048 | Cite as

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

Research Article

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 

References

  1. 1.
    Bramwell VH. Osteosarcomas and other cancers of bone. Curr Opin Oncol. 2000;12:330–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009;125:229–34.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kager L, Zoubek A, Kastner U, Kempf-Bielack B, Potratz J, Kotz R, et al. Skip metastases in osteosarcoma: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol. 2006;24:1535–41.CrossRefPubMedGoogle Scholar
  4. 4.
    Leary SE, Wozniak AW, Billups CA, Wu J, McPherson V, Neel MD, et al. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children’s Research Hospital experience. Cancer. 2013;119:2645–53.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  6. 6.
    Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.CrossRefPubMedGoogle Scholar
  7. 7.
    Croce CM, Calin GA. MiRNAs, cancer, and stem cell division. Cell. 2005;122:6–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Gregory RI, Shiekhattar R. MicroRNA biogenesis and cancer. Cancer Res. 2005;65:3509–12.CrossRefGoogle Scholar
  9. 9.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.CrossRefPubMedGoogle Scholar
  11. 11.
    Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jones KB, Salah Z, Del MS, Galasso M, Gaudio E, Nuovo GJ, et al. MiRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 2012;72:1865–77.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Namlos HM, Meza-Zepeda LA, Baroy T, Ostensen IH, Kresse SH, Kuijjer ML, et al. Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One. 2012;7:e48086.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Cheng C, Chen ZQ, Shi XT. MicroRNA-320 inhibits osteosarcoma cells proliferation by directly targeting fatty acid synthase. Tumour Biol. 2014;35:4177–83.CrossRefPubMedGoogle Scholar
  15. 15.
    Shen L, Chen XD, Zhang YH. MicroRNA-128 promotes proliferation in osteosarcoma cells by downregulating PTEN. Tumour Biol. 2014;35:2069–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Godlewski J, Bronisz A, Nowicki MO, Chiocca EA, Lawler S. MicroRNA-451: a conditional switch controlling glioma cell proliferation and migration. Cell Cycle. 2010;9:2742–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Bandres E, Bitarte N, Arias F, Agorreta J, Fortes P, Agirre X, et al. MicroRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res. 2009;15:2281–90.CrossRefPubMedGoogle Scholar
  18. 18.
    Wang R, Wang ZX, Yang JS, Pan X, De W, Chen LB. MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting Ras-related protein 14 (RAB14). Oncogene. 2011;30:2644–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Bergamaschi A, Katzenellenbogen BS. Tamoxifen downregulation of miR-451 increases 14-3-3zeta and promotes breast cancer cell survival and endocrine resistance. Oncogene. 2012;31:39–47.CrossRefPubMedGoogle Scholar
  20. 20.
    Li E, Zhang J, Yuan T, Ma B. MiR-145 inhibits osteosarcoma cells proliferation and invasion by targeting ROCK1. Tumour Biol. 2014Google Scholar
  21. 21.
    Reczko M, Maragkakis M, Alexiou P, Grosse I, Hatzigeorgiou AG. Functional microRNA targets in protein coding sequences. Bioinformatics. 2012;28:771–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Betel D, Koppal A, Agius P, Sander C, Leslie C. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol. 2010;11:R90.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Liu T, Zhou W, Zhang F, Shi G, Teng H, Xiao J, et al. Knockdown of IRX2 inhibits osteosarcoma cell proliferation and invasion by the AKT/MMP9 signaling pathway. Mol Med Rep. 2014;10:169–74.PubMedGoogle Scholar
  24. 24.
    Li G, Hattermann K, Mentlein R, Mehdorn HM, Held-Feindt J. The transmembrane chemokines CXCL16 and CX3CL1 and their receptors are expressed in human meningiomas. Oncol Rep. 2013;29:563–70.PubMedGoogle Scholar
  25. 25.
    Na KY, Kim HS, Jung WW, Sung JY, Kalil RK, Kim YW, et al. CXCL16 and CXCR6 in Ewing sarcoma family tumor. Hum Pathol. 2014;45:753–60.CrossRefPubMedGoogle Scholar
  26. 26.
    Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell. 2006;125:1253–67.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhu XC, Dong QZ, Zhang XF, Deng B, Jia HL, Ye QH, et al. MicroRNA-29a suppresses cell proliferation by targeting SPARC in hepatocellular carcinoma. Int J Mol Med. 2012;30:1321–6.PubMedGoogle Scholar
  28. 28.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Wang T, Zang WQ, Li M, Wang N, Zheng YL, Zhao GQ. Effect of miR-451 on the biological behavior of the esophageal carcinoma cell line EC9706. Dig Dis Sci. 2013;58:706–14.CrossRefPubMedGoogle Scholar
  30. 30.
    Xu H, Mei Q, Shi L, Lu J, Zhao J, Fu Q. Tumor-suppressing effects of miR451 in human osteosarcoma. Cell Biochem Biophys. 2014;69:163–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Liu F, Zhang Y, Tang H, Zhou X, Wu Z, Tang D, et al. CXC chemokine ligand 16, inversely correlated with CD99 expression in Hodgkin Reed-Sternberg cells, is widely expressed in diverse types of lymphomas. Oncol Rep. 2013;30:783–92.PubMedGoogle Scholar
  32. 32.
    Hattermann K, Held-Feindt J, Ludwig A, Mentlein R. The CXCL16-CXCR6 chemokine axis in glial tumors. J Neuroimmunol. 2013;260:47–54.CrossRefPubMedGoogle Scholar

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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