Details

Autor(en) / Beteiligte

• Han, Cecil
• Liu, Yunhua
• Wan, Guohui
• Choi, Hyun Jin
• Zhao, Luqing
• Ivan, Cristina
• He, Xiaoming
• Sood, Anil K.
• Zhang, Xinna
• Lu, Xiongbin

Titel

The RNA-Binding Protein DDX1 Promotes Primary MicroRNA Maturation and Inhibits Ovarian Tumor Progression

Ist Teil von

• Cell reports (Cambridge), 2014-09, Vol.8 (5), p.1447-1460

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •DDX1 is a regulatory component of the Drosha microprocessor•DDX1 promotes the expression of a subset of miRNAs•Knockdown of DDX1 promotes ovarian tumor invasion and metastasis•Levels of DDX1 are correlated with clinical outcome in patients with ovarian cancer Posttranscriptional maturation is a critical step in microRNA (miRNA) biogenesis during which specific recruitment and processing of individual primary miRNAs (pri-miRNAs) might be conferred by regulatory RNA-binding proteins. Han et al. now show that the RNA-binding protein DDX1 promotes the expression of a subset of ovarian-cancer-associated miRNAs. DDX1 levels are positively correlated with clinical outcome in patients with ovarian cancer. Inhibiting DDX1 promotes ovarian tumor progression. The results demonstrate that DDX1 is a key modulator in miRNA maturation and ovarian tumor suppression.