DNA methylation level of promoter region of activating transcription factor 5 in glioma

Abstract

Abstract:Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches have shown that the expression level of activating transcription factor 5 (ATF5) was frequently increased in glioma and its acetylation level was related to glioma. The purposes of this study were to explore the methylation level of ATF5 in clinical glioma tissues and to explore the effect of ATF5 methylation on the expression of ATF5 in glioma. Methylation of the promoter region of ATF5 was assayed by bisulfite-specific polymerase chain reaction (PCR) sequencing analysis in 35 cases of glioma and 5 normal tissues. Quantitative real-time PCR (qRT-PCR) was also performed to detect ATF5 mRNA expression in 35 cases of glioma and 5 normal tissues. Clinical data were collected from the patients and analyzed. The percentages of methylation of the ATF5 gene in the promoter region in healthy control, patients with well-differentiated glioma, and those with poorly differentiated glioma were 87.78%, 73.89%, and 47.70%, respectively. Analysis of the methylation status of the promoter region of the ATF5 gene showed a gradually decreased methylation level in poorly differentiated glioma, well-differentiated glioma, and normal tissues (P<0.05). There was also a significant difference between well-differentiated glioma and poorly differentiated glioma (P<0.05). ATF5 mRNA expression in glioma was significantly higher than that in the normal tissues (P<0.05). This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma.

Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients

“…However, the cohorts underlying the assessment of ATF5 expression in GBM were too small to define clinical subgroups 23,25. Furthermore, reports on LGA are scarce, comprising only few specimens and merging different WHO grades and tumor entities into the same group for further analysis,26 which limits the scientific significance. Therefore, we extended these observations by examining a large panel of 79 GBM, 40 LGA, and 10 NB for ATF5 expression.…”

“…However, such interference did not cause any visible effects on NB or cultured astrocytes 21,23,24. Although data concerning ATF5 expression in GBM are available,23,25 data on ATF5 expression in LGA are scarce 26. ATF5 has been shown to be significantly upregulated especially in invasive ductal and invasive lobular breast carcinomas,27 and its overexpression enhances the migratory and invasive behavior of A549 lung carcinoma cells 28.…”

The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer

“…It could be hypothesized that these functions mediated by ATF5 in cancer also occur in nontransformed cells, but this hypothesis has yet to be tested. ATF5 expression is also significantly associated with tumor grade in several cancer types [ 48 , 49 ]. In addition to these functions is the novel role for ATF5 as a structural protein where it facilitates formation of the centrosome, thereby suggesting ATF5 may promote proper mitotic function [ 50 ].…”

“…ATF5 expression was also shown to be upregulated in GBMs and anaplastic gliomas relative to low grade gliomas and normal cortical tissue, indicating that ATF5 expression may be associated with more malignant glioma phenotypes [ 53 ]. Indeed, analysis of ATF5 promoter methylation in glioma revealed that there is a substantial decrease in promoter methylation in high grade gliomas relative to low grade gliomas and normal tissue, thereby suggesting alterations in promoter methylation drive aberrant ATF5 expression in high grade gliomas [ 49 ]. In addition, ATF5 was shown to mediate the survival response to serum deprivation and staurosporine treatment in C6 glioma cells supporting the notion that ATF5 has an oncogenic and prosurvival role in gliomas [ 33 ].…”

DNA Methylation as a Future Therapeutic and Diagnostic Target in Rheumatoid Arthritis

“…In the human genome, there are approximately 30,000 CpG islands. Importantly, approximately 60–70% of annotated gene promoters are associated with CpG islands, suggesting that methylation of CpG islands is an important component of gene expression regulation [16]. The relationship between non-mutagenic environmental factors, influencing epigenetics alteration and subsequently pathology, has been examined primarily through the studies of the DNA methylation pattern in animal models [17].…”