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J Neurooncol. 2017 May;133(1):59-68. doi: 10.1007/s11060-017-2425-9. Epub 2017 Apr 19.

MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT.

Nie E1, Jin X1, Wu W1, Yu T1, Zhou X1, Shi Z1,2, Zhang J1, Liu N1,3, You Y4,5.

Author information

1
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
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.
3
Chinese Glioma Cooperative Group (CGCG), Nanjing, China.
4
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. yypl9@njmu.edu.cn.
5
Chinese Glioma Cooperative Group (CGCG), Nanjing, China. yypl9@njmu.edu.cn.

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.

KEYWORDS:

Glioblastoma; MGMT; Temozolomide resistance; miR-198

PMID:
28425046
DOI:
10.1007/s11060-017-2425-9
[Indexed for MEDLINE]

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