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

Kosar Babaei,Roya Khaksar,Seyed Hossein Mirpour,Kourosh Delpasand,Hooman Hashemian,Mohammad Taghi Ashoobi,Tahereh Zeinali,Arman Keymoradzadeh,Fereshteh Talebinasab,Hoora Naebi,Ahmadreza Bandegi,Seyedeh Elham Norollahi,Hossein Hemmati,Pirouz Samidoust

doi:10.1051/bmdcn/2019090422

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.

Highlights

Colorectal cancer is one of the leading causes of death worldwide and is one of the most common malignancies in the digestive tract [1]
Another form is family one which is about 25% of the patients are in this group and is considered as hereditary form which is often familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC)
Because of the different mechanism of different genes in different pathways, we selected mutY homolog E. coli (MUTYH), Krüppel-like factor 6 gene (KLF6), KLF4 and WNT1genes in order to discuss their importance in carcinogenesis and tumorigenesis in Colorectal cancer (CRC).Intrestingly, all these mentioned genes have a noticeable impression in cancer progression

Summary

Introduction

Colorectal cancer is one of the leading causes of death worldwide and is one of the most common malignancies in the digestive tract [1]. Epithelial cells become malignant in colon cells [4] Often, these changes are caused in oncogene, tumor suppressor and DNA repair genes. Can be mentioned other genes such as the inactivation of the p53 tumor suppressor gene seen in the late stages of adenocarcinoma, which contributes to the metastasis process. Another form is family one which is about 25% of the patients are in this group and is considered as hereditary form which is often familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC)

Epigenetic and cancer

Involvement of certain genes

Conclusions

Findings

Conflicts of interest statement