FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O⁶-methylguanine-DNA methyltransferase-dependent manner
10.4196/kjpp.2019.23.6.475
- Author:
Wenbing SHANGGUAN
1
;
Xuyang LV
;
Nan TIAN
Author Information
1. Institute of Molecular Medicine, Life Science College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China. tiannanlux@126.com
- Publication Type:Original Article
- Keywords:
Drug Resistance;
Glioma;
Long-noncoding RNA;
Methylation;
Temozolomide
- MeSH:
Brain Neoplasms;
Drug Resistance;
Drug Therapy;
Glioma;
Humans;
Methylation;
Prognosis;
Promoter Regions, Genetic;
RNA;
RNA, Long Noncoding;
Treatment Failure
- From:The Korean Journal of Physiology and Pharmacology
2019;23(6):475-482
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
