Alterations of epigenetics and microRNAs in cancer and cancer stem cell

ALTERATIONS OF DNA METHYLATION AND HISTONE MODIFICATION IN CANCER Epigenetics is an acquired modification of methylation and/or acetylation of chromatin DNA or histone proteins, which regulates downstream gene expression. Epigenetic alterations can be induced by aging, chronic inflammation and viral infection. Aberrant DNA methylation and/or histone modification at the CpG island promoter may induce inactivation of tumor suppressor genes and play critical roles in the initiation and progression of human cancer. In silico analysis is essential to investigate putative genetic and epigenetic elements of tumor suppressor genes such as Rb1 gene. This may contribute genetic and epigenetic information modulating tissue-specific transcripts and expression levels of genes (Hajjari et al., 2014). Genome-wide analysis of DNA methylation by BeadChip assay is quite useful to identify aberrantly methylated genes in human cancers. HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, and HOXA7 were identified as aberrantly methylated genes in human papillary thyroid cancers by genome-wide analysis of DNA methylation. In addition, papillary thyroid cancers with preferential methylation were significantly associated with mutations of the BRAF/RAS oncogenes. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer (Kikuchi et al., 2013). In 2010, the International Human Epigenome Consortium (IHEC) was established to coordinate the production of reference maps of human epigenomes for key cellular states (http:// www.ihec-epigenomes.net/). In order to gain substantial coverage of the human epigenome, the IHEC is planning to decipher at least 1000 epigenomes. These multilayer-omics analyses including genome, epigenome, transcriptome, proteome and metabolome are important for elucidating the molecular carcinogenesis and for exploring biomarkers and therapeutic targets for human cancers (Kanai and Arai, 2014).