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The RNA-binding protein DDX1 promotes primary microRNA maturation and inhibits ovarian tumor progression.

Abstract
Posttranscriptional maturation is a critical step in microRNA (miRNA) biogenesis that determines mature miRNA levels. In addition to core components (Drosha and DGCR8 [DiGeorge syndrome critical region gene 8]) in the microprocessor, regulatory RNA-binding proteins may confer the specificity for recruiting and processing of individual primary miRNAs (pri-miRNAs). Here, we identify DDX1 as a regulatory protein that promotes the expression of a subset of miRNAs, including five members in the microRNA-200 (miR-200) family and four miRNAs in an eight-miRNA signature of a mesenchymal ovarian cancer subtype. A majority of DDX1-dependent miRNAs are induced after DNA damage. This induction is facilitated by the ataxia telangiectasia mutated (ATM)-mediated phosphorylation of DDX1. Inhibiting DDX1 promotes ovarian tumor growth and metastasis in a syngeneic mouse model. Analysis of The Cancer Genome Atlas (TCGA) reveals that low DDX1 levels are associated with poor clinical outcome in patients with serous ovarian cancer. These findings suggest that DDX1 is a key modulator in miRNA maturation and ovarian tumor suppression.
AuthorsCecil Han, Yunhua Liu, Guohui Wan, Hyun Jin Choi, Luqing Zhao, Cristina Ivan, Xiaoming He, Anil K Sood, Xinna Zhang, Xiongbin Lu
JournalCell reports (Cell Rep) Vol. 8 Issue 5 Pg. 1447-60 (Sep 11 2014) ISSN: 2211-1247 [Electronic] United States
PMID25176654 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Biomarkers, Tumor
  • MicroRNAs
  • DDX1 protein, mouse
  • DDX1 protein, human
  • DEAD-box RNA Helicases
Topics
  • Adenocarcinoma (diagnosis, metabolism)
  • Animals
  • Biomarkers, Tumor (genetics, metabolism)
  • Cell Line, Tumor
  • DEAD-box RNA Helicases (genetics, metabolism)
  • DNA Damage
  • Female
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs (genetics, metabolism)
  • Ovarian Neoplasms (diagnosis, metabolism)

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