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Article

miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6

  • Authors:
    • Zhongrun Qian
    • Sunhai Zhou
    • Zhiyi Zhou
    • Xi Yang
    • Shuanlin Que
    • Jin Lan
    • Yongming Qiu
    • Yingying Lin
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China, Department of Neurosurgery, The First Hospital of Longyan Affiliated to Fujian Medical University, Longyan, Fujian, P.R. China
  • Pages: 2941-2950
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    Published online on: September 19, 2017
       https://doi.org/10.3892/or.2017.5970
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Abstract

Temozolomide (TMZ), as a kind of alkylating agent, is widely utilized for the treatment of glioblastoma (GBM). However, temozolomide resistance (TR) often develops quickly and results in tumor recurrence and poor outcome. Recent advances have demonstrated that miRNAs exert critical roles in chemoresistance. Downregulation of miR‑146b‑5p promotes glioma cell proliferation, reduces apoptosis, and correlates with poor survival of patients. Nonetheless, the function of miR‑146b‑5p in temozolomide resistance remains unclear. In the present study, we successfully generated U87 and U251‑TR cells, and found that miR‑146b‑5p was downregulated in TR cells. Overexpression of miR‑146b‑5p restored sensitivity of U87/U251‑TR cells to TMZ by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6). The levels of TRAF6 were inversely related to miR‑146b‑5p levels, and overexpression of TRAF6 in miR‑146b‑5p‑OE cells enhanced the resistance against TMZ. Moreover, temozolomide-resistant GBM cells had a higher level of phosphorylated protein kinase B (AKT) and P65. Overexpression of miR‑146b‑5p or TRAF6 knockdown significantly decreased the level of p‑AKT and p‑p65. Collectively, our data demonstrated that miR‑146b‑5p, as a tumor suppressor, mediated temozolomide resistance in GBM cells through negatively regulating TRAF6 expression, indicating that miR‑146b‑5p and its targeted genes would be potential therapeutic targets for glioma therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Qian Z, Zhou S, Zhou Z, Yang X, Que S, Lan J, Qiu Y and Lin Y: miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6. Oncol Rep 38: 2941-2950, 2017.
APA
Qian, Z., Zhou, S., Zhou, Z., Yang, X., Que, S., Lan, J. ... Lin, Y. (2017). miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6. Oncology Reports, 38, 2941-2950. https://doi.org/10.3892/or.2017.5970
MLA
Qian, Z., Zhou, S., Zhou, Z., Yang, X., Que, S., Lan, J., Qiu, Y., Lin, Y."miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6". Oncology Reports 38.5 (2017): 2941-2950.
Chicago
Qian, Z., Zhou, S., Zhou, Z., Yang, X., Que, S., Lan, J., Qiu, Y., Lin, Y."miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6". Oncology Reports 38, no. 5 (2017): 2941-2950. https://doi.org/10.3892/or.2017.5970
Copy and paste a formatted citation
x
Spandidos Publications style
Qian Z, Zhou S, Zhou Z, Yang X, Que S, Lan J, Qiu Y and Lin Y: miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6. Oncol Rep 38: 2941-2950, 2017.
APA
Qian, Z., Zhou, S., Zhou, Z., Yang, X., Que, S., Lan, J. ... Lin, Y. (2017). miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6. Oncology Reports, 38, 2941-2950. https://doi.org/10.3892/or.2017.5970
MLA
Qian, Z., Zhou, S., Zhou, Z., Yang, X., Que, S., Lan, J., Qiu, Y., Lin, Y."miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6". Oncology Reports 38.5 (2017): 2941-2950.
Chicago
Qian, Z., Zhou, S., Zhou, Z., Yang, X., Que, S., Lan, J., Qiu, Y., Lin, Y."miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6". Oncology Reports 38, no. 5 (2017): 2941-2950. https://doi.org/10.3892/or.2017.5970
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