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MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT

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Abstract

Glioblastoma is one of the most frequent and aggressive brain tumors. Accumulating evidence indicates that microRNAs are involved in glioma proliferation, invasion and drug resistance. Previous studies showed that miR-198 is downregulated in glioblastoma. However, the function of miR-198 in glioblastoma is still unclear. In this study, we report that miR-198 levels were greatly downregulated in glioblastoma specimens and decreased expression of miR-198 was associated with poor prognosis in patients with glioblastoma. And overexpression of miR-198 increased chemosensitivity to temozolomide in vitro and in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct target of miR-198, and miR-198 overexpression prevented the protein translation of MGMT. Furthermore, overexpression of MGMT restored miR-198-induced chemosensitivity to temozolomide. Moreover, the protein levels of MGMT were upregulated in clinical glioblastoma specimens and inversely correlated with miR-198 levels. In conclusion, our studies revealed that MiR-198 induces chemosensitivity in glioblastoma by targeting MGMT and that miR-198 may be used as a new diagnostic marker and therapeutic target for glioblastoma in the future.

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Funding

This work is supported by National Natural Science Foundation of China (81472362). The National Key Research and Development Plan (No. 2016YFC0902500).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Er Nie, Xin Jin, Weining Wu, Tianfu Yu, Xu Zhou, Zhumei Shi, Junxia Zhang, Ning Liu & Yongping You

  2. State Key Lab of Reproductive Medicine, Department of Pathology, Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing, 210029, China

    Zhumei Shi

  3. Chinese Glioma Cooperative Group (CGCG), Nanjing, China

    Ning Liu & Yongping You

Authors
  1. Er Nie
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  2. Xin Jin
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  3. Weining Wu
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  4. Tianfu Yu
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  5. Xu Zhou
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  6. Zhumei Shi
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  7. Junxia Zhang
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Correspondence to Yongping You.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Animal experiments were approved by the Animal Management Rule of the Chinese Ministry of Health (documentation 55, 2001) and were in accordance with the approved guidelines and the experimental protocol of The First Affiliated Hospital of Nanjing Medical University (Nanjing, China).

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Nie, E., Jin, X., Wu, W. et al. MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT. J Neurooncol 133, 59–68 (2017). https://doi.org/10.1007/s11060-017-2425-9

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