MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT
MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT
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DOI：
10.1007/s11060-017-2425-9
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发表时间：
2017-05-01
影响因子：
3.9
通讯作者：
You, Yongping
中科院分区：
文献类型：
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作者：
Nie, Er;Jin, Xin;You, Yongping
胶质母细胞瘤是最常见和最具侵袭性的脑肿瘤之一。越来越多的证据表明 microRNA 参与神经胶质瘤的增殖、侵袭和耐药性。先前的研究表明，miR-198 在胶质母细胞瘤中表达下调。然而，miR-198在胶质母细胞瘤中的功能仍不清楚。在这项研究中，我们报告说，胶质母细胞瘤标本中 miR-198 水平大幅下调，并且 miR-198 表达降低与胶质母细胞瘤患者预后不良相关。 miR-198 的过度表达增加了体外和体内对替莫唑胺的化疗敏感性。 O-6-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 被确定为 miR-198 的直接靶标，miR-198 过表达可阻止 MGMT 的蛋白翻译。此外，MGMT 的过度表达恢复了 miR-198 诱导的替莫唑胺化疗敏感性。此外，MGMT 的蛋白水平在临床胶质母细胞瘤标本中上调，并且与 miR-198 水平呈负相关。总之，我们的研究表明，miR-198通过靶向MGMT诱导胶质母细胞瘤的化疗敏感性，并且miR-198未来可能被用作胶质母细胞瘤的新诊断标记物和治疗靶点。
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. O-6-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.