MiR-520a-3p inhibits malignant progression of epithelial ovarian cancer by targeting SUV39H1 expression

Hum Cell. 2021 Mar;34(2):570-578. doi: 10.1007/s13577-020-00455-2. Epub 2020 Nov 16.

Abstract

Downregulation of microRNA-520a-3p (miR-520a-3p) has been demonstrated in several cancers, and miR-520a-3p has been shown to inhibit tumor progression, indicating its potential role as a tumor suppressor. In this study, we found that miR-520a-3p was also downregulated in epithelial ovarian cancer (EOC) tissues and cell lines. Functional assays showed that ectopic expression of miR-520a-3p suppressed EOC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) and induced cell cycle arrest in vitro. Similarly, overexpression of miR-520a-3p inhibited tumor growth and metastasis in vivo. Mechanistically, suppressor of variegation 39H1 (SUV39H1) was identified as a novel target of miR-520a-3p through biomedical databases and dual-luciferase reporter assay. Subsequently, SUV39H1 was observed to be negatively regulated by miR-520a-3p at the mRNA and protein levels, and inversely correlated with miR-520a-3p expression in EOC tissues. Furthermore, overexpression of SUV39H1 reversed the suppressive effects of miR-520a-3p in EOC cells. Collectively, these results suggest that the miR-520a-3p/SUV39H1 axis may contribute to EOC cell proliferation and metastasis, revealing miR-520a-3p as a potential therapeutic target for the treatment of EOC.

Keywords: Epithelial ovarian cancer; Metastasis; Proliferation; SUV39H1; miR-520a-3p.

MeSH terms

  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Disease Progression
  • Female
  • Gene Expression / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Tumor Suppressor*
  • Humans
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Molecular Targeted Therapy
  • Neoplasm Metastasis / genetics*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*

Substances

  • MIRN520 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • SUV39H1 protein, human
  • Methyltransferases