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

FEBS Lett. 2018 Jul;592(13):2308-2322. doi: 10.1002/1873-3468.13106. Epub 2018 Jun 21.

Abstract

DDX3X is a multifunctional RNA helicase with documented roles in different cancer types. Here, we demonstrate that DDX3X plays an oncogenic role in breast cancer cells by modulating the cell cycle. Depletion of DDX3X in MCF7 cells slows cell proliferation by inducing a G1 phase arrest. Notably, DDX3X inhibits expression of Kruppel-like factor 4 (KLF4), a transcription factor and cell cycle repressor. Moreover, DDX3X directly interacts with KLF4 mRNA and regulates its splicing. We show that DDX3X-mediated repression of KLF4 promotes expression of S-phase inducing genes in MCF7 breast cancer cells. These findings provide evidence for a novel function of DDX3X in regulating expression and downstream functions of KLF4, a master negative regulator of the cell cycle.

Keywords: DDX3X; KLF4; RNA helicase; breast cancer; cell cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Cycle / genetics*
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • DEAD-box RNA Helicases / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics*
  • MCF-7 Cells

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • DDX3X protein, human
  • DEAD-box RNA Helicases