Hypermethylation-mediated inactivation of miR-124 predicts poor prognosis and promotes tumor growth at least partially through targeting EZH2/H3K27me3 in ESCC

Clin Exp Metastasis. 2019 Aug;36(4):381-391. doi: 10.1007/s10585-019-09974-1. Epub 2019 Jun 13.

Abstract

Accumulating evidences indicated that some microRNAs (miRNAs) play a critical role during the carcinogenesis. In the present study, we found that miR-124 is down-regulated in esophageal squamous cell carcinoma (ESCC) tissues. Three miR-124 encoding genes, including mir-124-1, mir-124-2, and mir-124-3, harboring CpG islands undergo methylation-mediated miR-124 inactivation in ESCC tissues. The methylation status of all these three genes was negatively associated with the expression of miR-124. The low expression of miR-124 and the hypermethylation of mir-124-1 and mir-124-3 were associated with the clinico-pathological parameters indicating the poor prognosis. In addition, promoter methylation of all three genes plus low expression of miR-124 was the independent poor prognostic marker for ESCC patients. In conclusion, miR-124 may function as a tumor suppressive miRNA, and hypermethylation-mediated inactivation of miR-124 may be useful for a poor prognostic marker for ESCC patients.

Keywords: Esophageal squamous cell carcinoma; Methylation; miR-124; mir-124-1; mir-124-2; mir-124-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Methylation*
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / mortality
  • Esophageal Squamous Cell Carcinoma / pathology
  • Genes, Tumor Suppressor
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • MicroRNAs / physiology*
  • Prognosis
  • Promoter Regions, Genetic

Substances

  • MIRN124 microRNA, human
  • MicroRNAs
  • Jumonji Domain-Containing Histone Demethylases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein