A Study on the Aberrant Methylation of Colorectal Cancer MLH1 Gene

Abstract

The aim of this paper is to study the mechanism of MLH1 gene expression and regulation in colorectal cancer, and to clarify the impact of 5' end CpG island aberrant methylation on the regulation of MLH1 gene expression. RT-PCR assay was used to detect the expression of MLH1 gene mRNA in 10 colon cancer cell strains. 62 fresh colorectal adenocarcinoma samples and paired distal normal mucosa were selected in our hospital. They comprised 37 males and 25 females aging 32 to 67 years old with the mean of 43.6. The cellular RNA was extracted, and immunohistochemistry assay was used to detect the expression of MLH1 protein in colorectal cancer, and MSP method was utilized to examine the methylation status of the first exon of MLH1 gene in the tissues. In the 10 cell strains, only the MLH1 mRNAs of SW480 and Caco2 were expressed, and no MLH1 mRNA expression was detected in the other eight strains. The expression level of MLH1 mRNA in the 62 cases of cancer tissue was higher than that in the paired normal mucosa, and MLH1 protein was mainly expressed in the cytoplasm. The expression level of MLH1 protein in adenocarcinoma tissues was significantly higher than that in the paired normal tissue (P<0.01), while the methylation level of cancer tissues was statistically significantly lower than that of the paired normal mucosa (P<0.05). Aberrant DNA methylation dominates the regulation of the MLH1 gene expression changes in colorectal cancer. The results herein provide a theoretical basis for clarifying the differential expressions of MLH1 in colorectal cancer in vitro and in vivo.