Reduced miR-125a-5p Level in Non-Small-Cell Lung Cancer Is Associated With Tumour Progression

Open Biol. 2018 Oct 10;8(10):180118. doi: 10.1098/rsob.180118.

Abstract

Emerging evidence suggests that microRNAs (miRNAs) serve an important role in tumourigenesis and development. Although the low expression of miR-125a-5p in non-small-cell lung cancer (NSCLC) has been reported, the underlying mechanism remains unknown. In the current study, the low expression of miR-125a-5p in NSCLC was verified in paired cancer tissues and adjacent non-tumour tissues. Furthermore, the CpG island in the miR-125a-5p region was hypermethylated in the tumour tissues, and the hypermethylation was negatively correlated with 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 Suv39H1 expression and decrease the H3K9me3 levels. On the other hand, 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 NSCLC cells, which suppressed cell migration, invasion and proliferation in vitro and inhibited cancer progression in vivo Thus, we found that the epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in NSCLC, suggesting that miR-125a-5p might not only have the potential prognostic value as a tumour biomarker but also be a potential therapeutic target in NSCLC.

Keywords: Suv39H1; miR-125a-5p; non-small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Movement
  • Cell Proliferation
  • CpG Islands
  • Disease Progression
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIRN125 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • SUV39H1 protein, human
  • Methyltransferases