MiR203 Lost Suppressor Genes Function in the Process of Barrett’s Esophagus Carcinogenesis Because of High Methylation in Promoter

Liu Tianyu

doi:10.11648/j.cmr.20190801.14

Abstract

This study was designed to explore the role of MiR203 promoter methylation in the process of Barrett’s esophagus carcinogenesis. RT-PCR was used to detect the expression levels of miRNA-203 in Barrett’s esophagus, esophageal cancer and normal esophageal mucosa cell lines, before and after the treatment of demethylation. MiR203 promoter methylation levels in these cell lines were measured by Methylation Specific PCR (MSP). Immunohistochemistry was used to test the expression and distribution of K-Ras, a target of miR203, in esophageal cancer, BE and normal esophagus tissues. The following results were found based on the above methods. MiR203 expression levels were reduced obviously in Barrett esophagus and esophageal cancer cells than normal esophageal cells, the difference was statistically significant (P=0.003). After demethylation treatment, miR203 expression levels were significantly increased in Barrett's esophagus and esophageal cancer cells, the differences were statistically significant (P=0.03). MSP results showed that miR203 promoter changed to be low-methylation or non-methylation after demethylation treatment. In conclusion, MiR203 in Barrett's esophagus and esophageal cancer cells reduced expression is related to its Promoter methylation, miR203 promoter methylation throughout the carcinogenesis of Barrett's esophagus, it may become a key molecular biomarker in process of Barrett esophagus cancerous, and may become the prevention and treatment targets of Barrett esophagus carcinogenesis.

Highlights

Barrett’s esophagus (BE) was referred to a pathological phenomenon, what occurred in the lower esophagus, that simple columnar epithelium metaplasia replaced the stratified squamous epithelium, whatever with or without intestinal metaplasia, and which accompanied by special types of intestinal metaplasia was domestic grandpa as Esophageal Adenocarcinoma (EAC) of precancerous lesions
RT-PCR tests in BE and esophageal cancer tissues showed that miR203 expression levels were both lower in them than adjacent normal esophageal tissues, and it was more lower in esophageal cancer tissues than BE (Figure 3)
Results of Methylation Specific PCR (MSP) in cell lines showed that methylation and permethylation was found in miR203 promoter in BE and esophageal cancer cell lines, and non-methylation in normal cell lines (Figure 4-A)

Summary

Introduction

Barrett’s esophagus (BE) was referred to a pathological phenomenon, what occurred in the lower esophagus, that simple columnar epithelium metaplasia replaced the stratified squamous epithelium, whatever with or without intestinal metaplasia, and which accompanied by special types of intestinal metaplasia was domestic grandpa as Esophageal Adenocarcinoma (EAC) of precancerous lesions. Epigenetics means the heritable changes in gene expression, but not in DNA sequence. The change way includes DNA methylation, chromatin remodeling, histone modifications and non-coding RNA, etc. DNA methylation is one of the important mechanisms of epigenetics [2], it is closely related to the development of cancer [3, 4]. MicroRNAs (miRNA) is a kind of non-coding small RNAs, with about 22 to 28 nucleotides, it can regulate cell proliferation, differentiation and apoptosis, and it can regulate the development of cancer by suppressor genes or oncogenes. The epigenetics regulation in miRNA expression plays an important role in the development of cancer, so this study was designed to observe the relationship between miR203 promoter methylation and BE carcinogenesis

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