title: Whole DNA methylome profiling in lung cancer cells before and after epithelial-to-mesenchymal transition.
abstract: BACKGROUND
  Metastatic 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  DNA 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.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1112892497119603.
authors.forename: Fatao
authors.initials: F
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Daizhan
authors.initials: D
authors.lastname: Zhou
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Kan
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Niu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Liming
authors.initials: L
authors.lastname: Tao
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Taiyuan RD, Shanghai 200031, PR China. lxzhan@sibs.ac.cn.
authors.forename: Lixing
authors.initials: L
authors.lastname: Zhan
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D008745:Methylation; D006899:Mixed Function Oxygenases; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases