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  • Title: Epigenetic alterations of the Igf2 promoter and the effect of miR‑483‑5p on its target gene expression in esophageal squamous cell carcinoma.
    Author: Zhang H, Shi X, Chang W, Li Y, Wang L, Wang L.
    Journal: Mol Med Rep; 2018 Feb; 17(2):2251-2256. PubMed ID: 29207103.
    Abstract:
    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 α, 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.
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