FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O6-methylguanine-DNA methyltransferase-dependent manner
FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O6-methylguanine-DNA methyltransferase-dependent manner
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FoxD2-AS1 是神经胶质瘤的预后因素，并以 O-6-甲基鸟嘌呤-DNA 甲基转移酶依赖性方式促进替莫唑胺耐药
DOI：
10.4196/kjpp.2019.23.6.475
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发表时间：
2019-11-01
影响因子：
2
通讯作者：
Tian, Nan
中科院分区：
文献类型：
--
作者：
Shangguan, Wenbing;Lv, Xuyang;Tian, Nan
神经胶质瘤是最常见的脑肿瘤，预后很差。虽然替莫唑胺（TMZ）为基础的化疗显着提高胶质瘤患者的生存率，对这种化合物的耐药性通常导致胶质瘤治疗失败。长链非编码RNA（LncRNA）FoxD 2-AS 1（FoxD 2-AS 1）的过表达被鉴定为促进胶质瘤的发展，但其在TMZ耐药中的作用尚不清楚。本研究发现FoxD 2-AS 1在复发性胶质瘤中过表达，高表达FoxD 2-AS 1与患者预后不良显著相关。O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的甲基化在FoxD 2-AS 1高表达患者中的频率明显较低。FoxD 2-AS 1的敲除可降低胶质瘤细胞的增殖和转移能力，并提高胶质瘤细胞对TMZ的敏感性。此外，FoxD 2-AS 1的敲除可诱导MGMT启动子区的高甲基化。我们的数据表明，FoxD 2-AS 1是一种临床相关的LncRNA，通过调节MGMT启动子区域的甲基化状态介导TMZ耐药。
Glioma is the most common brain tumor with a dismal prognosis. While temozolomide (TMZ) based chemotherapy significantly improves survival in glioma patients, resistance against this compound commonly leads to glioma treatment failure. Overexpression of long-noncoding RNA (LncRNA) FoxD2 adjacent opposite strand RNA 1 (FoxD2-AS1) was identified to promote glioma development, but the role in TMZ resistance remains unclear. In this paper, we found that FoxD2-AS1 was overexpressed in recurrent glioma, high FoxD2-AS1 expression was significantly correlated with poor patient outcome. Methylation of O-6-methylguanine-DNA methyltransferase (MGMT) is significantly less frequent in high FoxD2-AS1 expression patients. Knockdown of FoxD2-AS1 decreased the proliferation, metastatic ability of glioma cells and promote the sensitivity to TMZ in glioma cells. Furthermore, knockdown of FoxD2-AS1 induced hypermethylation of the promoter region of MGMT. Our data suggested that FoxD2-AS1 is a clinical relevance LncRNA and mediates TMZ resistance by regulating the methylation status of the MGMT promoter region.