miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple-negative breast cancer

Cell Signal. 2018 Apr:44:33-42. doi: 10.1016/j.cellsig.2018.01.013. Epub 2018 Jan 12.

Abstract

Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region (3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that Daam1 was the target gene of miR-613. Overexpressed miR-613 reduced the protein level of Daam1, weakened RhoA activity, and retarded the cell migration, cell invasion and colony formation of TNBC cells. Overexpression of Daam1 or RhoA rescued cell migration and invasion in miR-613-overexpressed TNBC cells, but failed to reverse colony formation. MiR-613 was significantly downregulated in breast cancer tissues compared with that in adjacent normal tissues. This downregulation in TNBC tissues and lymphnode metastatic breast cancer tissues was more obvious than that in non-TNBC tissues and non-metastatic cancer tissues, respectively. MiR-613 weakens the resistance of TNBC cells against paclitaxel rather than adriamycin, cyclophosphamide, docetaxel, and kaempferol. Taken together, miR-613 is involved in cell migration and invasion of TNBC cells via targeting Daam1/RhoA signaling pathway.

Keywords: Daam1; Invasion; Migration; TNBC; miR-613.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cyclophosphamide / pharmacology
  • Docetaxel / pharmacology
  • Down-Regulation
  • Doxorubicin / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Kaempferols / pharmacology
  • Lymphatic Metastasis
  • MCF-7 Cells
  • MicroRNAs / metabolism*
  • Microfilament Proteins
  • Neoplasm Invasiveness
  • Paclitaxel / pharmacology
  • Signal Transduction
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • DAAM1 protein, human
  • Kaempferols
  • MIRN613 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • RHOA protein, human
  • Docetaxel
  • kaempferol
  • Doxorubicin
  • Cyclophosphamide
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein
  • Paclitaxel