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 (P<0.01); however, they dropped significantly after surgical removal (P<0.01). Compared with adjacent normal tissues, miR-373-3p also showed significant up-regulation in cancer tissues (P<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. Large tumor suppressor 2 (LATS2) and oxidation resistance 1(OXR1) are predicted to be targets of miR-373-3p by the bioinformatics method. They are the genes in the Hippo and the p53 signaling pathway, respectively. Their respective upstream genes, neurofibromatosis type 2 (NF2) and Jun Kinase, and the downstream genes, transcriptional co-activator with PDZ-binding motif (TAZ) and caspase 9, 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 p53 signaling pathways play important roles during the miR-373-3p mediating ESCC development process.
Keywords: 53; Epigenetic modification; Hippo; esophageal squamous cell carcinoma; microRNA-373.