Tumor Biology

, Volume 37, Issue 5, pp 5769–5773 | Cite as

RETRACTED ARTICLE: Downregulation of microRNA-217 and microRNA-646 acts as potential predictor biomarkers in progression, metastasis, and unfavorable prognosis of human osteosarcoma

  • Afshin Taheri Azam
  • Reza Bahador
  • Hamid Hesarikia
  • Mohammadreza Shakeri
  • Ali YeganehEmail author
Original Article


Despite the progress in therapeutic targets, it remains dissatisfactory for most osteosarcoma patients with metastasis or recurrence osteosarcoma. Therefore, it is required to determine the involved mechanisms of osteosarcoma. The aim of this study was to investigate the expression level of MiR-217 and miR-646 and also their association with clinicopathological features in patients with osteosarcoma. Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues, and then quantitative real-time PCR was applied to evaluate the expression level of microRNAs. Our result suggested that miR-217 expression was remarkably deceased in osteosarcoma bone tissue when compared with noncancerous bone tissues (mean ± SD 5.32 ± 1.231, 2.01 ± 0.78; P = 0.024) and miR-646 expression decreased in osteosarcoma bone tissue in comparison with normal tissues (mean ± SD 4.56 ± 1.45, 1.76 ± 1.24; P = 0.041). Our findings indicated that decreased expression of MiR-217 and miR-646 was strongly correlated with high tumor, node, and metastasis (TNM) stage (P = 0.015, P = 0.002) and large cancer diameter (P = 0.041, P = 0.053). Kaplan-Meier survival and log-rank analysis indicated that shorter overall survival was strongly linked to decreased expression of miR-217 and miR-646 (log-rank test P = 0.034, P = 0.026). In terms of miR-217, multivariate Cox proportional hazards model analysis has showed that reduction of miR-217 expression (P = 0.001), TNM stage (P = 0.046), and lymph node metastasis (P = 0.006) were independently linked to a short-time survival of patients. In terms of miR-646, low expression of miR-646 (P = 0.021), TNM stage (P = 0.052), and tumor size (P = 0.043) were independently associated with poor survival of patients as prognostic factors. Our findings suggested that downregulation of MiR-217 and miR-646 was associated with progression of osteosarcoma. MiR-217 and miR-646 may play a key role in suppression of tumor in osteosarcoma and would be applied as a novel therapeutic agent.


Osteosarcoma MiRNAs Pathology Metastasis Patient 



We thank Dr. Heydari, Dr. Mousavi and Dr. Alizadeh for their technical assistance in this article.

Conflicts of interest



  1. 1.
    Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer. 2009;115:1531–43.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.CrossRefPubMedGoogle Scholar
  3. 3.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  4. 4.
    Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S. Role of Dicer and Droshafor endothelial microRNA expression and angiogenesis. Circ Res. 2007;101:59–68.CrossRefPubMedGoogle Scholar
  5. 5.
    Finnerty JR, Wang WX, Hébert SS. The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases. J Mol Biol. 2010;402(3):491–509.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, et al. MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 2011;17(24):7574–83.CrossRefPubMedGoogle Scholar
  7. 7.
    Wu X, Zhong D, Gao Q, Zhai W, Ding Z, Wu J. MicroRNA-34a inhibits human osteosarcoma proliferation by downregulating ether a go-go 1 expression. Int J Med Sci. 2013;10:676–82.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11:136–46.CrossRefPubMedGoogle Scholar
  9. 9.
    Bao YP, Yi Y, Peng LL, Fang J, Liu KB, Li WZ. Roles of microRNA-206 in osteosarcoma pathogenesis and progression. Asian Pac J Cancer Prev. 2013;14:3751–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Tang M, Lin L, Cai H, Tang J, Zhou Z. MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma. Onco Targets Ther. 2013;6:833–8.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Zhao G, Cai C, Yang T. MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One. 2013;8(1), e53906.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Huang J, Gao K, Lin J. MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61. Tumor Biol. 2014;35(2):1095–100.CrossRefGoogle Scholar
  13. 13.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.CrossRefPubMedGoogle Scholar
  14. 14.
    Cimino D, De Pitta C, Orso F, Zampini M, Casara S, Penna E, et al. MiR148b is a major coordinator of breast cancer progression in a relapse associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J. 2013;27:1223–35.CrossRefPubMedGoogle Scholar
  15. 15.
    Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM, Chen J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 2010;31:1726–33.CrossRefPubMedGoogle Scholar
  16. 16.
    Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 2009;11:R27.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wu XJ, Li Y, Liu D, Zhao LD, Bai B, Xue MH. MiR-27a as an oncogenic microRNA of hepatitis B virus-related hepatocellular carcinoma. Asian Pac J Cancer Prev. 2013;14:885–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Li W, Liu M, Feng Y. Downregulated miR-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nine one binding protein (NOB1). Br J Cancer. 2014;111(6):1188–200.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Shen L, Wang P, Yang J, Li X. MicroRNA-217 regulates WASF3 expression and suppresses tumor growth and metastasis in osteosarcoma. PLoS One. 2014;9(10), e109138.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Sun XH, Geng XL, Zhang J. Zhang C.miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2). Tumour Biol. 2015;36(3):2127–34.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Afshin Taheri Azam
    • 1
  • Reza Bahador
    • 2
  • Hamid Hesarikia
    • 3
  • Mohammadreza Shakeri
    • 2
  • Ali Yeganeh
    • 4
    Email author
  1. 1.Department of Orthopedics SurgeryIslamic Azad UniversityTehranIran
  2. 2.Department of Orthopaedic and Trauma SurgeryBirjand University of Medical SciencesBirjandIran
  3. 3.Trauma Research Center, Department of Orthopedics, Baqiyatallah HospitalBaqiyatallah University of Medical SciencesTehranIran
  4. 4.Department of Orthopedic Surgery, Rasoul Akram HospitalIran University of Medical SciencesTehranIran

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