DNMT3B Expression Might Contribute to Abnormal Methylation of RASSF1A in Lager Colorectal Adenomatous Polyps.

Xianmei Meng,Wei Zhang,Tong Dang,Kerui Gong,Na Liu,Guo Shao,Jingjie Zhang,Yanbin Jia

doi:10.1155/2020/1798729

Abstract

Background It is pretty well known that DNA methyltransferases (DNMTs) are actively involved in abnormal cell growth. The goal of the current study is to explore the correlation between DNMT expression and colorectal adenomatous polyps (CAPs). Method Twenty pairs of CAP samples with a diameter ≥ 10 mm and corresponding normal colorectal mucosa (NCM) tissues from patients were used in the present study. The expression levels and activity of DNA methyltransferases (DNMTs) were measured in the CAP tissues. The global methylation and the promoter methylation level of 3 kinds of tumour suppressor gene were detected. Results mRNA and protein levels of DNMT3B were found to be elevated in the CAP tissues compared with the control tissue. Additionally, the methylation of long interspersed nuclear elements-1 (LINE-1/L1) was decreased in the CAP tissue. Furthermore, methylation of the promoter of a tumour suppressor gene Ras association domain family 1A (RASSF1A) was increased in the CAP tissues, while the mRNA levels of RASSF1A were decreased. Conclusions These results suggest that the overexpression of DNMT3B may contribute to a role in the genesis of CAPs through the hypomethylation of chromosomes in the whole cell and promoter hypermethylation of RASSF1A.

Highlights

Colorectal cancer (CRC) ranks as the fifth and third most commonly diagnosed cancer in the Chinese and American populations [1, 2]
DNMT3B Expression Levels Increased in colorectal adenomatous polyps (CAPs) Tissues
Relative expression levels of DNMT3B mRNA were significantly higher in the CAP tissues than those in the normal colorectal mucosa (NCM) tissue (P < 0:05)

Summary

Introduction

Colorectal cancer (CRC) ranks as the fifth and third most commonly diagnosed cancer in the Chinese and American populations [1, 2]. Stryker et al revealed that a very small number of polyps that were initially 2–5 mm in diameter would eventually become invasive carcinomas. They suggested that the diminutive size of most of these polyps might be hyperplastic rather than adenomatous and, not at risk for malignant change. Methylation of the promoter of a tumour suppressor gene Ras association domain family 1A (RASSF1A) was increased in the CAP tissues, while the mRNA levels of RASSF1A were decreased. These results suggest that the overexpression of DNMT3B may contribute to a role in the genesis of CAPs through the hypomethylation of chromosomes in the whole cell and promoter hypermethylation of RASSF1A

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Conclusion