MUTYH and KLF6 gene expression fluctuations in tumor tissue and tumor margins tissues of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most important cancers in the world, and its prevalence varies depending on the geographical area. Genetically, tumor regeneration in CRC as a multi-step process involves activating mutations in protocogenes and losing the function of tumor suppressor genes as well as DNA repair and recovery genes. Occur in this way, our goal was to investigate the expression of KLF6 genes as a tumor suppressor and MUTYH involved in the DNA repair process in colorectal cancer. METHODS: This research was conducted during the years 2019-2018 in Razi Hospital, Rasht. The subjects included 30 tumoral and 30 non-tumoral tissues of colorectal cancer and 20 healthy controls. The real-time PCR method was used to investigate the gene expression. For data analysis by SPSS, parametric statistical tests ANOVA and T test and regression analysis were used and p value values less than 0.05 were considered significant. RESULTS: The expression of KLF6 gene in tumoral tissues showed a significant decrease compared to non-tumoral tissues (P = 0.04). Also, the expression of MUTYH gene in tumor tissue showed a significant decrease compared to non-tumoral (P = 0.02) and this decrease in MUTYH gene expression had a significant relationship with increasing tumor stage (P = 0.01). CONCLUSION: These findings suggest that decreased expression of KLF6 and MUTYH genes in the study population has a significant relationship with colorectal cancer and can be considered as tumor marker in diagnostic purpose.

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

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.