Reversal of aberrant cancer methylome and transcriptome upon direct reprogramming of lung cancer cells.
Recent reports on direct reprogramming of cancer cells (iPCs) which results in reduced tumorigenic potential has attributed the importance of epigenetics in tumorigenesis, but lacked genome-wide analysis. Here we describe successful generation of iPCs from non-small cell lung cancer (NSCLC) cell lines. Following reprogramming, they resembled embryonic stem and induced pluripotent stem cells in pluripotency markers expression, gene expression patterns and in vitro differentiation ability. Genome-wide methylation analysis revealed that aberrantly methylated promoters which were mostly developmental-associated genes and tumor suppressors; as well as commonly upregulated genes in NSCLC i.e. KRT19 and S100P were reversed in iPCs upon reprogramming. Also, the reversal of oncogenes and tumor suppressors status were partially explainable by DNA methylation. These findings suggest that DNA methylation patterns explain the downstream transcriptional effects, which potentially caused the reduced tumorigenicity in iPCs, thus providing evidence that reprogramming reverses the aberrantly dysregulated genes in NSCLC both epigenetically and transcriptionally.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Dashayini
D
Mahalingam
Chiou Mee
CM
Kong
Jason
J
Lai
Ling Lee
LL
Tay
Henry
H
Yang
Xueying
X
Wang
D014408:Biomarkers, Tumor; D002273:Carcinogens; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D059467:Transcriptome
D014408:Biomarkers, Tumor; D002273:Carcinogens