Skip to main content

Advertisement

Log in

Increased Expression of microRNA-199b-5p Associates with Poor Prognosis Through Promoting Cell Proliferation, Invasion and Migration Abilities of Human Osteosarcoma

  • Research
  • Published:
Pathology & Oncology Research

Abstract

MicroRNA (miR)-199b-5p has been reported to be upregulated in human osteosarcoma tissues and participate in the Notch signaling in osteosarcoma cells. This study was aimed to investigate the associations of miR-199b-5p expression with tumor progression of primary osteosarcoma, and to deepen the understanding of its involvement in carcinogenesis. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to detect expression levels of miR-199b-5p in 98 osteosarcoma and corresponding adjacent normal tissues. Then, the correlations of its expression with clinicopathological characteristics and patient prognosis were statistically analyzed. Moreover, in vitro assays were performed to assess the effects of miR-199b-5p on the proliferation, migration and invasion of two human osteosarcoma cell lines MG63 and U2OS. Compared to normal controls, miR-199b-5p expression was significantly upregulated in osteosarcoma tissues (P < 0.001). In addition, the expression levels of miR-199b-5p in osteosarcoma patients with high tumor grade (P = 0.008), positive metastasis (P = 0.001) and positive recurrence (P = 0.001) were markedly higher than those with low tumor grade, negative metastasis and negative recurrence. Moreover, osteosarcoma patients with high miR-199b-5p expression showed shorter overall survival (P < .001) and shorter disease-free survival (P < 0.001) than those with low expression. Furthermore, the inhibition of miR-199b-5p significantly suppressed cell proliferation, and reduced the migratory and invasive abilities of osteosarcoma cells. This study offer the convincing evidence for the first time that the increased expression of miR-199b-5p may play crucial roles in aggressive progression and poor prognosis of human osteosarcoma. miR-199b-5p may function as an oncogene by positively regulating the malignant potentials of this neoplasm.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Marina N, Gebhardt M, Teot L, Gorlick R (2004) Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9:422–441

    Article  PubMed  Google Scholar 

  2. Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G (2006) Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev 32:423–436

    Article  PubMed  Google Scholar 

  3. Bielack SS, Marina N, Ferrari S (2008) Osteosarcoma: the same old drugs or more? J Clin Oncol 26:3102–3103

    Article  PubMed  Google Scholar 

  4. Broadhead ML, Clark JC, Myers DE, Dass CR, Choong PF (2011) The molecular pathogenesis of osteosarcoma: a review. Sarcoma 2011:959248

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kansara M, Thomas DM (2007) Molecular pathogenesis of osteosarcoma. DNA Cell Biol 26:1–18

    Article  CAS  PubMed  Google Scholar 

  6. Carrington JC, Ambros V (2003) Role of microRNAs in plant and animal development. Science 301:336–338

    Article  CAS  PubMed  Google Scholar 

  7. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  8. Brodersen P, Voinnet O (2009) Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol 10:141–148

    Article  CAS  PubMed  Google Scholar 

  9. Garzon R, Marcucci G, Croce CM (2010) Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov 9:775–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  CAS  PubMed  Google Scholar 

  11. Ji F, Zhang H, Wang Y (2013) MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1. Bone 56:220–226

    Article  CAS  PubMed  Google Scholar 

  12. Pan W, Wang H, Jianwei R, Ye Z (2014) MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. Cell Physiol Biochem 33:402–412

    Article  CAS  PubMed  Google Scholar 

  13. Novello C, Pazzaglia L, Cingolani C (2013) miRNA expression profile in human osteosarcoma: role of miR-1 and miR-133b in proliferation and cell cycle control. Int J Oncol 42:667–675

    CAS  PubMed  Google Scholar 

  14. Zhang K, Zhang C, Liu L, Zhou J (2014) A key role of microRNA-29b in suppression of osteosarcoma cell proliferation and migration via modulation of VEGF. Int J Clin Exp Pathol 7:5701–5708

    PubMed  PubMed Central  Google Scholar 

  15. Shen L, Wang P, Yang J, Li X (2014) MicroRNA-217 regulates WASF3 expression and suppresses tumor growth and metastasis in osteosarcoma. PLoS ONE 9:e109138

    Article  PubMed  PubMed Central  Google Scholar 

  16. Geng S, Zhang X, Chen J, Liu X, Zhang H, Xu X, Ma Y, Li B, Zhang Y, Bi Z, Yang C (2014) The tumor suppressor role of miR-124 in osteosarcoma. PLoS ONE 9:e91566

    Article  PubMed  PubMed Central  Google Scholar 

  17. Flamant S, Ritchie W, Guilhot J (2010) Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia. Haematologica 95:1325–1333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Garzia L, Andolfo I, Cusanelli E (2009) MicroRNA-199b-5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma. PLoS ONE 4:e4998

    Article  PubMed  PubMed Central  Google Scholar 

  19. Won KY, Kim YW, Kim HS, Lee SK, Jung WW, Park YK (2013) MicroRNA-199b-5p is involved in the Notch signaling pathway in osteosarcoma. Hum Pathol 44:1648–1655

    Article  CAS  PubMed  Google Scholar 

  20. Fang C, Zhao Y, Guo B (2013) MiR-199b-5p targets HER2 in breast cancer cells. J Cell Biochem 114:1457–1463

    Article  CAS  PubMed  Google Scholar 

  21. Liu MX, Siu MK, Liu SS, Yam JW, Ngan HY, Chan DW (2014) Epigenetic silencing of microRNA-199b-5p is associated with acquired chemoresistance via activation of JAG1-Notch1 signaling in ovarian cancer. Oncotarget 5:944–958

    Article  PubMed  PubMed Central  Google Scholar 

  22. Li Z, Gu X, Fang Y, Xiang J, Chen Z (2012) microRNA expression profiles in human colorectal cancers with brain metastases. Oncol Lett 3:346–350

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Li Y, Bai H, Zhang Z (2014) The up-regulation of miR-199b-5p in erythroid differentiation is associated with GATA-1 and NF-E2. Mol Cell 37:213–219

    Article  CAS  Google Scholar 

  24. Bacci G, Bertoni F, Longhi A (2003) Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor. Cancer 97:3068–3075

    Article  CAS  PubMed  Google Scholar 

  25. Favreau AJ, Cross EL, Sathyanarayana P (2012) miR-199b-5p directly targets PODXL and DDR1 and decreased levels of miR-199b-5p correlate with elevated expressions of PODXL and DDR1 in acute myeloid leukemia. Am J Hematol 87:442–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang H, Cai X, Wang Y, Tang H, Tong D, Ji F (2010) MicroRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncol Rep 24:1363–1369

    CAS  PubMed  Google Scholar 

  27. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using realtime quantitative PCR and the 2 − ΔΔCt method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  28. Andolfo I, Liguori L, De Antonellis P (2012) The micro-RNA 199b-5p regulatory circuit involves Hes1, CD15, and epigenetic modifications in medulloblastoma. Neuro Oncol 14:596–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lauvrak SU, Munthe E, Kresse SH, Stratford EW, Namløs HM, Meza-Zepeda LA, Myklebost O (2013) Functional characterisation of osteosarcoma cell lines and identification of mRNAs and miRNAs associated with aggressive cancer phenotypes. Br J Cancer 109:2228–2236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of Interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Haibin Zeng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeng, H., Zhang, Z., Dai, X. et al. Increased Expression of microRNA-199b-5p Associates with Poor Prognosis Through Promoting Cell Proliferation, Invasion and Migration Abilities of Human Osteosarcoma. Pathol. Oncol. Res. 22, 253–260 (2016). https://doi.org/10.1007/s12253-015-9901-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-015-9901-3

Keywords

Navigation