DAAM1-mediated migration and invasion of ovarian cancer cells are suppressed by miR-208a-5p

Pathol Res Pract. 2019 Jul;215(7):152452. doi: 10.1016/j.prp.2019.152452. Epub 2019 May 14.

Abstract

Ovarian cancer (OvCa) has the highest morbidity among all gynecologic cancers worldwide, and its distant metastasis is one of main causes for the poor prognosis of OvCa patients. Our previous studies have reported that DAAM1-involved signaling pathways play vital roles in metastasis of breast cancer. However, whether DAAM1 participates in OvCa migration and/or invasion is still unknown. The impact of DAAM1 on cell migration and invasion in OvCa was evaluated by wound healing assay and Boyden chamber assay. The specific miRNA targeting DAAM1 was predicted by bioinformatics methods and verified by dual-luciferase activity assay. The miR-208a-5p expression levels in OvCa tissues and the impacts of miR-208a-5p on cell migration and invasion were also assessed, respectively. High expression of DAAM1 was associated with distant metastasis in OvCa. Silence of DAAM1 by siRNA blocked the migration and invasion of OVCAR-3 cells. MiR-208a-5p directly targeted DAAM1 and was shown a decreased expression in metastatic OvCa tissues. Elevated expression of miR-208a-5p inhibited the migration and invasion of OVCAR-3 cell which can be rescued by DAAM1 overexpression. Our data suggest that miR-208-5p/DAAM1 axis participates in OvCa migration and invasion and may be a novel clinical target to limit OvCa metastasis.

Keywords: DAAM1; Metastasis; Ovarian cancer; miR-208-5p.

MeSH terms

  • Cell Movement / physiology*
  • Cell Proliferation / physiology
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Wound Healing / physiology
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • DAAM1 protein, human
  • MIRN208 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • rho GTP-Binding Proteins