Epigenetic changes in colorectal cancer

Abstract

Epigenetic changes frequently occur in human colorectal cancer. Genomic global hypomethylation, gene promoter region hypermethylation, histone modifications, and alteration of miRNA patterns are major epigenetic changes in colorectal cancer. Loss of imprinting(LOI) is associated with colorectal neoplasia. Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation. HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment. Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer. This review is mainly focused on DNA methylation, histone modification, and microRNA changes in colorectal cancer.

Figure 1.. Folate and regulation of DNA synthesis, repair, and methylation.

Folate deficiency may decrease thymidylate syntheses, inhibit DNA repair, induce imbalance of DNA methylation, histone modification, and finally cause Carcinogenesis.

Figure 2.. Epigenetic regulation of gene expression.

Promoter region of tumor suppressor gene is unmethylated in normal cells and methylated in cancer cells. Filled cycles represent methylated DNA; unfilled cycles represent unmethylated DNA. Blue cylinder represents active histone modification; red cylinder represents repressive histone modification. 1, 2 and 3 represent exons 1, 2 and 3. HMT, histone methyltransferase; HAT, histone acetylase; DNMT, DNA methyltransferase; MBP, methyl-CpG binding protein; HDAC, histone deacetylase; TF, transcription factors; CA, co-activator; CR, co-repressor; Ac, acetylation; 4M, H3K4 methylation.