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

FEBS Letters
Ester CannizzaroT Kouzarides

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.

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Citations

Nov 2, 2019·Oncotarget·Esmee KoedootSylvia E Le Dévédec
Dec 4, 2020·International Journal of Molecular Sciences·Agnieszka Taracha-WisniewskaTomasz Wilanowski
Feb 26, 2021·Molecular Cancer·Jie MoBixiang Zhang
Apr 4, 2021·International Journal of Molecular Sciences·Olga Sergeeva, Timofei Zatsepin

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Methods Mentioned

BETA
immunoprecipitation
transfection
PCR
Chip
CLIP
RNA

Software Mentioned

GenomicAlignments
DAVID
GraphPad
prism
DAVID annotation
Ensembl
DAVID functional
DESeq2
Bioconductor DEXseq tool
tophat

Related Concepts