Overexpression of miR‑214 promotes the progression of human osteosarcoma by regulating the Wnt/β‑catenin signaling pathway

  • Authors:
    • Xun‑Bing Zhu
    • Zhong‑Chuan Zhang
    • Guan‑Sheng Han
    • Jun‑Zhu Han
    • Da‑Peng Qiu
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  • Published online on: February 14, 2017     https://doi.org/10.3892/mmr.2017.6203
  • Pages: 1884-1892
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Abstract

The aberrant expression of microRNA (miR)‑214 contributes to the regulation of normal and cancer cell biology, and is associated with human malignancies, however, it can operate in a contradictory manner. The role of miR‑214 in osteosarcoma remains to be fully elucidated. The aim of the present study was to investigate the effects of miR‑214 on osteosarcoma progression and tumor cell proliferation, and examine the molecular mechanism underlying osteosarcoma. The level of miR‑214 was determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis in osteosarcoma and matched paracancerous tissues, and in human osteosarcoma cancer cell lines. The roles of miR‑214 in cell proliferation, survival and cell cycle were analyzed using miR‑214 lentivirus (LV‑miR‑214)‑infected osteosarcoma cells. In addition, the downstream target proteins in the Wnt/β‑catenin signaling pathway were evaluated using western blot analysis in the LV‑miR‑214‑infected cells. The LV‑miR‑214‑infected MG63 cells were also treated with exogenous β‑catenin for 24, 48 and 72 h, respectively, following which the expression of β‑catenin was measured using western blot analysis and survival was determined using a 3‑(4,5‑cimethylthiazol‑2‑yl)‑2,5‑diphenyl tetrazolium bromide (MTT) assay. The results of the RT‑qPCR analysis showed that the expression level of miR‑214 was significantly higher in the osteosarcoma tissues, compared with that in the matched paracancerous tissues, and the same was observed in the osteosarcoma cell lines. The MG63, Saos‑2 and U2OS cells were infected with the hsa‑mir‑214 lentivirus for 48 h, and the levels of miR‑214 were significantly upregulated in the human osteosarcoma cancer cells. The overexpression of miR‑214 in the MG‑63 and Saos‑2 cells promoted cell growth, and treatment of the cells with specific antisense‑microRNA oligonucleotides (AMOs) for miR‑214 for indicated durations reversed the effects of miR‑214. Additionally, the AMO‑treated MG63 cells showed G0/G1 phase arrest, suggesting that miR‑214 contributed to regulation of the cell cycle. In addition, the results of western blot analysis showed that, in the miR‑214 lentivirus‑infected cells, the levels of cyclin‑D1, c‑myc and lymphoid enhancer‑binding factor‑1 were significantly increased, compared with those in the control lentivirus‑infected cancer cells. Of note, infection with the miR‑214 lentivirus did not affect the levels of Wnt1, Wnt2, Wnt4, Axin or glycogen synthase kinase β in the U2OS cells, whereas the expression levels of β‑catenin in the MG63 cells and Saos‑2 cells were significantly increased. The addition of exogenous β‑catenin effectively reversed the efficiency of miR‑214‑specific AMOs, which was detected using an MTT assay. These data suggested the critical role of miR‑214 in human osteosarcoma via regulation of the Wnt/β‑catenin signaling pathway and demonstrated that miR‑214 is as an oncogene for human osteosarcoma.
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April-2017
Volume 15 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhu XB, Zhang ZC, Han GS, Han JZ and Qiu DP: Overexpression of miR‑214 promotes the progression of human osteosarcoma by regulating the Wnt/β‑catenin signaling pathway. Mol Med Rep 15: 1884-1892, 2017
APA
Zhu, X., Zhang, Z., Han, G., Han, J., & Qiu, D. (2017). Overexpression of miR‑214 promotes the progression of human osteosarcoma by regulating the Wnt/β‑catenin signaling pathway. Molecular Medicine Reports, 15, 1884-1892. https://doi.org/10.3892/mmr.2017.6203
MLA
Zhu, X., Zhang, Z., Han, G., Han, J., Qiu, D."Overexpression of miR‑214 promotes the progression of human osteosarcoma by regulating the Wnt/β‑catenin signaling pathway". Molecular Medicine Reports 15.4 (2017): 1884-1892.
Chicago
Zhu, X., Zhang, Z., Han, G., Han, J., Qiu, D."Overexpression of miR‑214 promotes the progression of human osteosarcoma by regulating the Wnt/β‑catenin signaling pathway". Molecular Medicine Reports 15, no. 4 (2017): 1884-1892. https://doi.org/10.3892/mmr.2017.6203