Epigenetic alterations of the Igf2 promoter and the effect of miR-483-5p on its target gene expression in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most widespread malignancies in China. MicroRNAs (miRNAs/miRs) are endogenous evolutionarily-conserved small non-coding RNAs that are able to regulate ESCC formation and deterioration by negatively regulating specific target genes. In the present study, the expression levels of miR-483-5p and its associated mRNAs were measured by quantitative polymerase chain reaction (PCR) analysis, and the methylation levels of the insulin-like growth factor 2 (Igf2) promoter were detected via the methylation-specific PCR method in serum and tissues from patients with ESCC. The results demonstrated that the expression level of miR-483-5p was significantly upregulated in preoperative serum and cancer tissues from patients with ESCC (P<0.01), and the miR-483-5p expression levels were correlated with the tumor, node, metastasis stage (P<0.05) and lymph node metastasis (P<0.05). In addition, the mRNA levels of miR-483-5p target genes (Rho GDP dissociation inhibitor , activated leukocyte cell adhesion molecule, and suppressor of cytokine signaling 3) in cancer tissues were significantly decreased compared with adjacent non-cancerous tissues. These results indicated that miR-483-5p and its target genes may be involved in the developmental process of ESCC. The Igf2 levels in cancer tissues were significantly increased compared with adjacent non-cancerous tissues (P<0.01). Additionally, the methylation levels of the Igf2 promoter region were 31.82 and 54.55% in cancer tissues and adjacent non-cancerous tissues, respectively, suggesting that low methylation of the Igf2 gene promoter region may promote the expression of Igf2 and miR-483-5p; this, in turn, induces the degradation of miR-483-5p target genes, and leads to the upregulation of oncogenes and the downregulation of tumor suppressors, which promotes the development of ESCC.