Abstract
BackgroundMetastatic lung cancer is one of the leading causes of cancer death. In recent years, epithelial-to-mesenchymal transition (EMT) has been found to contribute to metastasis, as it enables migratory and invasive properties in cancer cells. Previous genome-wide studies found that DNA methylation was unchanged during EMT induced by TGF-β in AML12 cells. In this study, we aimed to discover EMT-related changes in DNA methylation in cancer cells, which are poorly understood.MethodsWe employed a next-generation sequencing-based method, MSCC (methyl-sensitive cut counting), to investigate DNA methylation during EMT in the A549 lung cancer cell line.ResultsWe found that methylation levels were highly correlated to gene expression, histone modifications and small RNA expression. However, no differentially methylated regions (DMRs) were found in A549 cells treated with TGF-β for 4 h, 12 h, 24 h and 96 h. Additionally, CpG islands (CGIs) showed no overall change in methylation levels, and at the single-base level, almost all of the CpGs showed conservation of DNA methylation levels. Furthermore, we found that the expression of DNA methyltransferase 1, 3a, 3b (DNMT1, DNMT3a, DNMT3b) and ten-eleven translocation 1 (TET1) was altered after EMT. The level of several histone methylations was also changed.ConclusionsDNA methylation-related enzymes and histone methylation might have a role in TGF-β-induced EMT without affecting the whole DNA methylome in cancer cells. Our data provide new insights into the global methylation signature of lung cancer cells and the role of DNA methylation in EMT.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1112892497119603
Highlights
Lung cancer is one of the most common causes of cancer-related death [1]
We report the relationship between DNA methylation, histone modifications and gene expression in lung cancer cells, and we describe the weak effect of epithelialto-mesenchymal transition (EMT) on the whole DNA methylome
After induction with TGF-β for 1 day and 4 days, the A549 cells gradually changed from an epithelial to elongated mesenchymal phenotype (Figure 1a)
Summary
Lung cancer is one of the most common causes of cancer-related death [1]. Metastasis and the related genetic and epigenetic changes are the main cause of the high death rate from lung cancer [5]. The migratory and invasive properties imparted by EMT (epithelial-to-mesenchymal transition) are known to be essential for metastasis [6]. Metastatic lung cancer is one of the leading causes of cancer death. Epithelialto-mesenchymal transition (EMT) has been found to contribute to metastasis, as it enables migratory and invasive properties in cancer cells. Previous genome-wide studies found that DNA methylation was unchanged during EMT induced by TGF-β in AML12 cells. We aimed to discover EMT-related changes in DNA methylation in cancer cells, which are poorly understood
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