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KMID : 0811720190230060475
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Korean Journal of Physiology & Pharmacology
2019 Volume.23 No. 6 p.475 ~ p.482
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FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O6-methylguanine-DNA methyltransferase-dependent manner
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Shangguan Wenbing
Lv Xuyang
Tian Nan
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Abstract
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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 O6-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.
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KEYWORD
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Drug Resistance, Glioma, Long-noncoding RNA, Methylation, Temozolomide
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