miR-205-3p Functions as a Tumor Suppressor in Ovarian Carcinoma

Reprod Sci. 2020 Jan;27(1):380-388. doi: 10.1007/s43032-019-00047-y. Epub 2020 Jan 6.

Abstract

Ovarian cancer (OC) represents the most lethal form of gynaecologic cancers in developed countries. To develop a better therapeutic against OC, characterizing new classes of molecular regulators such as microRNAs (miRNAs) involved in OC tumorigenesis becomes immensely important. We used human OC cell lines to study the expression pattern of miRNA-205-3p. We then employed miRNA-205-3p mimic and inhibitor to elucidate its functional role in OC cells. Downstream target of miRNA-205-3p was characterized in OC cells with luciferase gene reporter assay and Western blotting. Its functional role in OC was also investigated with the siRNA approach. Lastly, we assessed the expression change of miRNA-205-3p and its newly identified target in human OC tissues. miR-205-3p was downregulated in five human OC lines tested. Over-expressing miR-205-3p reduced OC cell proliferation and migration. MAPK10 was identified as a direct target of miR-205-3p. Knocking down MAPK10 suppressed OC cell growth and migration. In contrast, knocking down miR-205-3p promoted clonogenicity of primary ovary cells. In clinical samples, miR-205-3p and MAPK10 expressed inversely in accordance with their expression patterns in OC cells. miR-205-3p was shown as a novel tumor suppressor in OC via inhibiting the MAPK10 pathway. This new finding may inspire new personalized treatment for OC.

Keywords: HeyA8; MAPK10; Ovarian cancer; SK-OV-3; miR-205-3p.

MeSH terms

  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism*
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology

Substances

  • MIRN205 microRNA, human
  • MicroRNAs