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DDX3X RNA helicase affects breast cancer cell cycle progression by regulating expression of KLF4

Ester Cannizzaro1, Andrew John Bannister1, Namshik Han1

  • 1Department of Pathology and Gurdon Institute, University of Cambridge, Cambridge, UK.

FEBS Letters
|May 22, 2018
PubMed

Insights

The DDX3X RNA helicase promotes breast cancer cell growth by inhibiting KLF4, a cell cycle repressor. DDX3X

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • DDX3X is an RNA helicase implicated in various cancers.
  • Its specific role in breast cancer progression requires further elucidation.

Purpose of the Study:

  • To investigate the function of DDX3X in breast cancer cell cycle regulation.
  • To identify downstream targets and mechanisms of DDX3X action.

Main Methods:

  • Depletion of DDX3X in MCF7 breast cancer cells.
  • Analysis of cell cycle progression.
  • Assessment of Kruppel-like factor 4 (KLF4) expression and mRNA splicing.
  • Evaluation of S-phase inducing gene expression.

Main Results:

  • DDX3X depletion induced G1 phase arrest and slowed proliferation in MCF7 cells.
  • DDX3X was found to inhibit KLF4 expression.
  • DDX3X directly interacted with KLF4 mRNA, regulating its splicing.
  • DDX3X-mediated KLF4 repression promoted S-phase gene expression.

Conclusions:

  • DDX3X plays an oncogenic role in breast cancer by modulating the cell cycle.
  • DDX3X regulates breast cancer cell proliferation through KLF4 inhibition and altered mRNA splicing.
  • This study reveals a novel mechanism for DDX3X in breast cancer, involving KLF4 regulation.
Keywords:
DDX3XKLF4RNA helicasebreast cancercell cycle

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