MicroRNA-373 promotes the development of esophageal squamous cell carcinoma by targeting and .

Introduction: MicroRNA373 was highly expressed in many tumors including esophageal cancer. However, its molecular mechanism is still unclear, especially epigenetic modification, in esophageal squamous cell carcinoma (ESCC).

Methods: In this study, we investigated serum levels of the miR-371-373 cluster in ESCC patients before and after surgical removal, and further focused on the expression level of miR-373-3p in tumor tissues of ESCC patients and its target genes. In addition, the epigenetic alterations of miR-373-3p promoter was analyzed.

Results: The expression levels of miR-371-5p and miR-373-3p were significantly increased in preoperative serum of ESCC patients compared with that of healthy volunteers (<0.01); however, they dropped significantly after surgical removal (<0.01). Compared with adjacent normal tissues, miR-373-3p also showed significant up-regulation in cancer tissues (<0.05). The methylation levels of miR-373-3p promoter were 42.86% in ESCC cancer tissue and 66.67% in adjacent normal tissues. The low methylation of the miR-373-3p promoter may promote the expression of miR-373-3p. () and () are predicted to be targets of miR-373-3p by the bioinformatics method. They are the genes in the Hippo and the 53 signaling pathway, respectively. Their respective upstream genes, and , and the downstream genes, and , were also detected. The expression of all these genes were significantly decreased in ESCC cancer tissues compared with adjacent normal tissues.

Conclusions: This study shows that DNA epigenetic modification in the miR-373-3p promoter region and the Hippo and 53 signaling pathways play important roles during the miR-373-3p mediating ESCC development process.