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DDX 3X RNA helicase affects breast cancer cell cycle progression by regulating expression of KLF 4
Author(s) -
Cannizzaro Ester,
Bannister Andrew John,
Han Namshik,
Alendar Andrej,
Kouzarides Tony
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13106
Subject(s) - microbiology and biotechnology , cell cycle , rna helicase a , transcription factor , cell growth , cancer cell , chemistry , rna splicing , biology , cell , rna , cancer research , gene , cancer , helicase , biochemistry , genetics
DDX 3X is a multifunctional RNA helicase with documented roles in different cancer types. Here, we demonstrate that DDX 3X plays an oncogenic role in breast cancer cells by modulating the cell cycle. Depletion of DDX 3X in MCF 7 cells slows cell proliferation by inducing a G1 phase arrest. Notably, DDX 3X inhibits expression of Kruppel‐like factor 4 ( KLF 4), a transcription factor and cell cycle repressor. Moreover, DDX 3X directly interacts with KLF 4 mRNA and regulates its splicing. We show that DDX 3X‐mediated repression of KLF 4 promotes expression of S‐phase inducing genes in MCF 7 breast cancer cells. These findings provide evidence for a novel function of DDX 3X in regulating expression and downstream functions of KLF 4, a master negative regulator of the cell cycle.