Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer

Figure 2

Epigenetic silencing of NEIL1 expression in human cancer. (a) Map of the DNA methylation probes near the transcription start sites (TSSs) of the NEIL1 gene. The vertical arrows mark the position of the DNA methylation probes (CpG sites) or the translation initiation site (ATG). The thicker section in the exon region indicates the coding sequence. (b) Representative result showing the inverse correlation between DNA methylation at the NEIL1 CpG site and NEIL1 expression in cancer. A scatter plot analysis was performed for DNA methylation at the cg12978308 probe site and the NEIL1 mRNA expression level in HNSCC using data from the TCGA database. The Spearman rank correlation coefficient () and values were provided. A bivariate normal ellipse () was observed for normal tissue samples (red) and cancerous tissue samples (blue). (c) Effects of 5-aza-dC on the NEIL1 and NEIL3 expression levels in gastric cancer cell lines. The cell lines were treated with 5-aza-dC, and the NEIL1 and NEIL3 expression levels were measured using a real-time QRT-PCR analysis. The amounts of NEIL1 or NEIL3 transcripts normalized to the amount of GAPDH transcript are shown in the graph. The average expression levels in untreated cells were set at 1.0. Values are the mean ± standard error of three independent experiments. (d) Downregulation of NEIL1 protein expression in primary HNSCC. Representative results for NEIL1 expression in noncancerous head and neck epithelium (upper panel) and HNSCC (lower panel) are shown. Scale bar = 50 μm. (e) Impact of reduced NEIL1 expression on overall survival in primary breast cancer patients. The survival curves for breast cancer patients (,056) were based on data from the TCGA database and were generated using the Kaplan-Meier method. The patients were divided into two groups using a cut-off value of 0.5-fold the median NEIL1 expression value in noncancerous breast tissue. Log-rank: .

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