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Article Open Access

MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling

  • Authors:
    • Jun Liu
    • Lei Huang
    • Pengxiao Su
    • Tao Song
    • Wentao Zhang
    • Jinzhu Fan
    • Yang Liu
  • View Affiliations / Copyright

    Affiliations: Department of Hand and Foot Surgery and Reparative and Reconstructive Surgery, Orthopedic Hospital of The Second Hospital of Jilin University, Changchun, Jilin 130000, P.R. China, Department of Burns, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710054, P.R. China, Department of Orthopedics, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710054, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4113-4120
    |
    Published online on: January 17, 2018
       https://doi.org/10.3892/ol.2018.7814
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Abstract

A number of studies have attempted to elucidate the association between mircoRNAs (miRNAs/miRs) and cancer‑associated processes. The aim of the present study was to determine how miR‑499a‑5p intervenes in human osteosarcoma cell proliferation and differentiation. The cancerous tissues and adjacent non‑cancerous tissues of 62 patients with osteosarcoma (OS) were collected. miRNA microarray analysis revealed that 29 miRNAs were upregulated while 26 were downregulated, among which miR‑499a‑5p expression was the most decreased. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction demonstrated that the mRNA and protein expression of miR‑499a‑5p was lower, while that of protein phosphatase 1D (PPM1D) was higher in OS tissues compared with expression levels in normal tissues. Furthermore, miR‑499a‑5p expression was markedly decreased in the metastatic tumors and in those at stage III+IV compared with the non‑metastatic tumors and those at stage I, respectively. In addition, following transfection of the human OS MG‑63 cell line with an miR‑499a‑5p mimic, the expression of miR‑499a‑5p was elevated while the protein and mRNA expression of PPM1D was decreased. When combining these findings with the information obtained from the Targetscan predictive software, it was confirmed that PPM1D was targeted by miR‑499a‑5p. In MG‑63 cells transfected with an miR‑499a‑5p mimic, PPM1D‑associated downstream proteins phosphorylated protein kinase B (p‑Akt) and phosphorylated glycogen synthase kinase 3β (p‑GSK‑3β) were significantly downregulated compared with the negative control (NC) group, while the expression of p‑Akt and p‑GSK‑3β were significantly elevated in the tumor tissues compared with the adjacent non‑tumor tissues. Simultaneously, the growth and proliferation activity of MG‑63 cells were notably reduced when transfected with the miR‑499a‑5p mimic, compared with the NC group. Therefore, it may be concluded that miR‑499a‑5p suppresses OS cell proliferation and differentiation by targeting PPM1D through modulation of Akt/GSK‑3β signaling.
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Copy and paste a formatted citation
Spandidos Publications style
Liu J, Huang L, Su P, Song T, Zhang W, Fan J and Liu Y: MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling. Oncol Lett 15: 4113-4120, 2018.
APA
Liu, J., Huang, L., Su, P., Song, T., Zhang, W., Fan, J., & Liu, Y. (2018). MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling. Oncology Letters, 15, 4113-4120. https://doi.org/10.3892/ol.2018.7814
MLA
Liu, J., Huang, L., Su, P., Song, T., Zhang, W., Fan, J., Liu, Y."MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling". Oncology Letters 15.4 (2018): 4113-4120.
Chicago
Liu, J., Huang, L., Su, P., Song, T., Zhang, W., Fan, J., Liu, Y."MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling". Oncology Letters 15, no. 4 (2018): 4113-4120. https://doi.org/10.3892/ol.2018.7814
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Huang L, Su P, Song T, Zhang W, Fan J and Liu Y: MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling. Oncol Lett 15: 4113-4120, 2018.
APA
Liu, J., Huang, L., Su, P., Song, T., Zhang, W., Fan, J., & Liu, Y. (2018). MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling. Oncology Letters, 15, 4113-4120. https://doi.org/10.3892/ol.2018.7814
MLA
Liu, J., Huang, L., Su, P., Song, T., Zhang, W., Fan, J., Liu, Y."MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling". Oncology Letters 15.4 (2018): 4113-4120.
Chicago
Liu, J., Huang, L., Su, P., Song, T., Zhang, W., Fan, J., Liu, Y."MicroRNA‑499a‑5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling". Oncology Letters 15, no. 4 (2018): 4113-4120. https://doi.org/10.3892/ol.2018.7814
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