MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration

Exp Cell Res. 2017 Oct 15;359(2):394-404. doi: 10.1016/j.yexcr.2017.08.023. Epub 2017 Aug 17.

Abstract

Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. Our previous study has shown that MRTF-A promote the migration of MDA-MB-231 cells and WDR1 promotes breast cancer cell migration. But the exact molecular mechanism on metastasis is still not fully understood, we now report that WDR1 enhanced the effect of MRTF-A induced-MDA-MB-231 cell migration by promoting the expression of the EMT markers and migration markers via RhoA-MRTF-A signaling pathway. Importantly, WDR1 promoted the nuclear importion of MRTF-A by affecting the expression of nuclear transport protein importin. But WDR1 did not affect the expression of MRTF-A. Interestingly, MRTF-A promoted the expression of miR-206 via its promoter CArG box but miR-206 inhibits the migration of breast cancer cells through suppressing the expression of WDR1 and MRTF-A via targeted their 3'UTR. Our data thus provide important and novel insights into MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration.

Keywords: Breast cancer cell migration; EMT; MRTF-A; WDR1; miR-206.

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • Cell Movement
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition
  • Feedback, Physiological*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Promoter Regions, Genetic
  • Signal Transduction
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • 3' Untranslated Regions
  • Karyopherins
  • MIRN206 microRNA, human
  • MRTFA protein, human
  • MicroRNAs
  • Microfilament Proteins
  • Trans-Activators
  • WDR1 protein, human
  • RHOA protein, human
  • rhoA GTP-Binding Protein