Review article

Epigenetic profiling of MUTYH, KLF6, WNT1 and KLF4 genes in carcinogenesis and tumorigenesis of colorectal cancer

¹ Department of Biology, Islamic Azad University of Tonekabon Branch, Tonekabon, Iran
² Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
³ Razi Clinical Research Development Unit, Guilan University of Medical Sciences, Rasht, Iran
⁴ Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
⁵ Department of Surgery, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
⁶ Pediatric Diseases Research Center,Guilan University of Medical ciences, Rasht, Iran
⁷ School of Medicine, Kurdistan University of Mdical Ciences, Sanandaj, Iran
⁸ Department of Hematology and Oncology, Razi hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

^* Corresponding author. Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Razi Hospital, Sardar Jangal Street, Rasht, Iran. E-mail address: elnaz_Norollahi2000@yahoo.com (S. E. Norollahi).

Received: 9 August 2019
Accepted: 2 September 2019

Abstract

Colorectal cancer (CRC) is distinguished by epigenetic elements like DNA methylation, histone modification, histone acetylation and RNA remodeling which is related with genomic instability and tumor initiation. Correspondingly, as a main epigenetic regulation, DNA methylation has an impressive ability in order to be used in CRC targeted therapy. Meaningly, DNA methylation is identified as one of most important epigenetic regulators in gene expression and is considered as a notable potential driver in tumorigenesis and carcinogenesis through gene-silencing of tumor suppressors genes. Abnormal methylation situation, even in the level of promoter regions, does not essentially change the gene expression levels, particularly if the gene was become silenced, leaving the mechanisms of methylation without any response. According to the methylation situation which has a strong eagerness to be highly altered on CpG islands in carcinogenesis and tumorigenesis, considering its epigenetic fluctuations in finding new biomarkers is of great importance. Modifications in DNA methylation pattern and also enrichment of methylated histone signs in the promoter regions of some certain genes like MUTYH, KLF4/6 and WNT1 in different signaling pathways could be a notable key contributors to the upregulation of tumor initiation in CRC. These epigenetic alterations could be employed as a practical diagnostic biomarkers for colorectal cancer. In this review, we will be discuss these fluctuations of MUTYH, KLF4/6 and WNT1 genes in CRC.