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

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Tumor Biology

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.

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References

  1. Bramwell VH. Osteosarcomas and other cancers of bone. Curr Opin Oncol. 2000;12:330–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  6. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.

    Article  CAS  PubMed  Google Scholar 

  7. Croce CM, Calin GA. MiRNAs, cancer, and stem cell division. Cell. 2005;122:6–7.

    Article  CAS  PubMed  Google Scholar 

  8. Gregory RI, Shiekhattar R. MicroRNA biogenesis and cancer. Cancer Res. 2005;65:3509–12.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  10. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  15. Shen L, Chen XD, Zhang YH. MicroRNA-128 promotes proliferation in osteosarcoma cells by downregulating PTEN. Tumour Biol. 2014;35:2069–74.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  20. Li E, Zhang J, Yuan T, Ma B. MiR-145 inhibits osteosarcoma cells proliferation and invasion by targeting ROCK1. Tumour Biol. 2014

  21. Reczko M, Maragkakis M, Alexiou P, Grosse I, Hatzigeorgiou AG. Functional microRNA targets in protein coding sequences. Bioinformatics. 2012;28:771–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  32. Hattermann K, Held-Feindt J, Ludwig A, Mentlein R. The CXCL16-CXCR6 chemokine axis in glial tumors. J Neuroimmunol. 2013;260:47–54.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopedics, Ningbo Development Zone Center Hospital, Ningbo, 315800, China

    Fei Zhang

  2. Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 28 Fuxing Road, Shanghai, 200003, China

    Tielong Liu

  3. Department of Orthopedics, the Sixth People’s Hospital of Hangzhou, Hangzhou, 310007, China

    Wei Huang

  4. Department of Respiratory Medicine, Hospital of Longsai, Ningbo, 315200, China

    Meixia Sheng

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  1. Fei Zhang
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  2. Wei Huang
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  3. Meixia Sheng
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  4. Tielong Liu
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Correspondence to Tielong Liu.

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Fei Zhang and Wei Huang contributed equally to this paper.

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Zhang, F., Huang, W., Sheng, M. et al. MiR-451 inhibits cell growth and invasion by targeting CXCL16 and is associated with prognosis of osteosarcoma patients. Tumor Biol. 36, 2041–2048 (2015). https://doi.org/10.1007/s13277-014-2811-2

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  • DOI: https://doi.org/10.1007/s13277-014-2811-2

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