FoxD2-AS1is a prognostic factor in glioma and promotes temozolomide resistance in a O⁶-methylguanine-DNA methyltransferase-dependent manner

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.

Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

“…Recently, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been implicated in drug resistance of TMZ against glioma. A high promoter methylation status which means low MGMT activity predicts good response to TMZ chemotherapy and results in a longer survival period in glioma patients [31]. Therefore, we confirmed the methylation status of the MGMT promoter in U251/TMZ cells treated with curcumol and/or TMZ using MS-PCR.…”

“…For immunofluorescence staining neurospheres, the cells were fixed with 4% paraformaldehyde and incubated with antibodies against CD133 (18470- Protein samples were separated by 10%-12% SDS PAGE. Western blotting was performed based on a previous study [31]. The primary antibody to β-actin was purchased from Hua Bio (HuaAn Biotechnology Co., Ltd., Hangzhou, China), antibody to EphB3 was purchased from Invitrogen (Invitrogen, USA), the antibodies to MGMT, Nestin, SOX2, p21, CDKN1B were purchased from (Proteintech Group, Chicago, IL, USA), and the antibodies to EZH2 and Histone H3 (H3K27me3)…”

The DNA methylation-regulated MCTP1 activates the drug-resistance of esophageal cancer cells

“…As we know, the epigenetics modifications, such as the altered DNA methylation patterns can influence the expression of genes, and thus affect the cellular functions at every aspect [ 21 ]. More importantly, in the past decades, more and more studies have been shown that DNA methylation play roles in drug resistance of cancers [ 19 , 22 , 23 ]. However, it remains elusive how DNA hypermethylation correlates with the drug-resistance of cancers.…”

Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

“…Recently, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been implicated in drug resistance of TMZ against glioma. A high promoter methylation status which means low MGMT activity predicts good response to TMZ chemotherapy and results in a longer survival period in glioma patients [31]. Therefore, we con rmed the methylation status of the MGMT promoter in U251/TMZ cells treated with curcumol and/or TMZ using MS-PCR.…”