Epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in gastric cancer

J Cell Mol Med. 2018 Oct;22(10):4721-4731. doi: 10.1111/jcmm.13716. Epub 2018 Aug 17.

Abstract

Emerging evidence suggests that microRNAs (miRNAs) serve an important role in tumorigenesis and development. Although the low expression of miR-125a-5p in gastric cancer has been reported, the underlying mechanism remains unknown. In the current study, the low expression of miR-125a-5p in gastric cancer was verified in paired cancer tissues and adjacent non-tumour tissues. Furthermore, the GC islands in the miR-125a-5p region were hypermethylated in the tumour tissues. And the hypermethylation was negatively correlated with the miR-125a-5p expression. Target gene screening showed that the histone methyltransferase Suv39H1 was one of the potential target genes. In vitro studies showed that miR-125a-5p could directly suppress the Suv39H1 expression and decrease the H3K9me3 levels. On the other hand, the Suv39H1 could induce demethylation of miR-125a-5p, resulting in re-activation of miR-125a-5p. What is more, overexpessing miR-125a-5p could also self-activate the silenced miR-125a-5p in gastric cancer cells, which suppressed cell migration, invasion and proliferation in vitro and inhibited cancer progression in vivo. Thus, we uncovered here that the epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in gastric cancer, suggesting that miR-125a-5p might be not only the potential prognostic value as a tumour biomarker but also potential therapeutic targets in gastric cancer.

Keywords: Suv39H1; epigenetic silence; gastric cancer; miR-125a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Heterografts
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Male
  • Methylation
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • Mice, SCID
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • Histones
  • MIRN125 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • SUV39H1 protein, human
  • Methyltransferases