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Article

Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress

  • Authors:
    • Shinji Tsukamoto
    • Keiji Shimada
    • Kanya Honoki
    • Akira Kido
    • Manabu Akahane
    • Yasuhito Tanaka
    • Noboru Konishi
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan, Department of Pathology, Nara Medical University, Kashihara, Nara 634-8521, Japan, Department of Public Health, Health Management and Policy, Nara Medical University, Kashihara, Nara 634-8521, Japan
  • Pages: 1799-1806
    |
    Published online on: February 9, 2015
       https://doi.org/10.3892/or.2015.3788
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Abstract

Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis. Although UBQLN2 has been implicated in the pathogenesis of neurodegenerative diseases, it is also associated with mali­gnant tumors. Therefore, we examined whether UBQLN2 plays a role in human osteosarcoma. The human osteosarcoma cell line MG63 was transfected with UBQLN2 siRNA and cultured under hypoxic conditions. The rat osteosarcoma cell line COS1NR was inoculated into Fischer 344 rats, followed by injection of UBQLN2 siRNA with atelocollagen. An immunohistochemical analysis of UBQLN2 was performed using 34 cases of human high-grade osteosarcomas, and metastasis-free survival was estimated by the Kaplan-Meier method. Silencing of UBQLN2 by siRNA transfection under hypoxia led to activation of JNK and p38, resulting in induction of apoptosis in the osteosarcoma cell line MG63. Injection of UBQLN2 siRNA suppressed tumor growth in the rat osteosarcoma model, followed by apoptosis induction. The immunohistochemical examination revealed that high UBQLN2 expression was significantly associated with the unfavorable metastasis-free survival of osteosarcoma patients. UBQLN2 plays an important role in resistance to hypoxic stress and enhances tumor progression in osteosarcoma. UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma.
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Copy and paste a formatted citation
Spandidos Publications style
Tsukamoto S, Shimada K, Honoki K, Kido A, Akahane M, Tanaka Y and Konishi N: Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress. Oncol Rep 33: 1799-1806, 2015.
APA
Tsukamoto, S., Shimada, K., Honoki, K., Kido, A., Akahane, M., Tanaka, Y., & Konishi, N. (2015). Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress. Oncology Reports, 33, 1799-1806. https://doi.org/10.3892/or.2015.3788
MLA
Tsukamoto, S., Shimada, K., Honoki, K., Kido, A., Akahane, M., Tanaka, Y., Konishi, N."Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress". Oncology Reports 33.4 (2015): 1799-1806.
Chicago
Tsukamoto, S., Shimada, K., Honoki, K., Kido, A., Akahane, M., Tanaka, Y., Konishi, N."Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress". Oncology Reports 33, no. 4 (2015): 1799-1806. https://doi.org/10.3892/or.2015.3788
Copy and paste a formatted citation
x
Spandidos Publications style
Tsukamoto S, Shimada K, Honoki K, Kido A, Akahane M, Tanaka Y and Konishi N: Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress. Oncol Rep 33: 1799-1806, 2015.
APA
Tsukamoto, S., Shimada, K., Honoki, K., Kido, A., Akahane, M., Tanaka, Y., & Konishi, N. (2015). Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress. Oncology Reports, 33, 1799-1806. https://doi.org/10.3892/or.2015.3788
MLA
Tsukamoto, S., Shimada, K., Honoki, K., Kido, A., Akahane, M., Tanaka, Y., Konishi, N."Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress". Oncology Reports 33.4 (2015): 1799-1806.
Chicago
Tsukamoto, S., Shimada, K., Honoki, K., Kido, A., Akahane, M., Tanaka, Y., Konishi, N."Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress". Oncology Reports 33, no. 4 (2015): 1799-1806. https://doi.org/10.3892/or.2015.3788
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