Epigenetic gene silencing in colorectal cancer initiation and progression, review article

Document Type : Review article

Authors

Research center for non-communicable diseases, Jahrom University of medical sciences, Jahrom, Iran

Abstract

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. It develops through multiple steps that results from the progressive accumulation of mutations and epigenetic modifications in tumor suppressor genes (TSGs) and oncogenes. Epigenetic modifications play a fundamental role in the regulation and transcription of gene expression. These modifications involve DNA methylation of promoter regions, histone modifications, and non‐coding RNAs (ncRNAs) interventions. Histone modification and DNA methylation are involved in a complex network to maintain gene silencing lead to tumorigenesis. DNA methylation is methylated by DNA methyltransferases (DNMTs), which transfer the methyl group from S-adenosylmethionine (SAM) to generate patterns of genomic methylation that silence genes. In this review, we discuss the current and fast-growing knowledge about the contribution of the hypermethylation of several TSGs toward an understanding of molecular mechanisms of CRC. Methods. For this review article, the eligible studies were obtained by searching PubMed, SCOPUS, NCBI, and Ovid database with the MeSH terms combined with free terms. Results. We found evidence that DNA methyltransferases can induce DNA methylation in tumor suppressor genes (TSGs) resulting in cancer induction. Conclusion. The downregulation of TSGs expression might be responsible in promoting cancer induction.

Keywords


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