DDX1 as a regulatory component of the Drosha microprocessor (Bos taurus)

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1pri-miRNAOncogenic stressEpithelial-Mesenchymal Transition (EMT)and MetastasisEnhanced processing of DDX1-dependent miRNAsDNA damageATMDGCR8DROSHANBNRAD50MRE11ADDX1DDX1PDDX1pre-miRNA


Description

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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP2942(80337) with a 100.0% conversion rate.

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Bibliography

  1. Han C, Liu Y, Wan G, Choi HJ, Zhao L, Ivan C, He X, Sood AK, Zhang X, Lu X; ''The RNA-binding protein DDX1 promotes primary microRNA maturation and inhibits ovarian tumor progression.''; Cell Rep, 2014 PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
87366view09:52, 22 July 2016MaintBotadded missing graphids
87224view14:43, 19 July 2016SusanOntology Term : 'regulatory pathway' added !
80868view15:29, 30 June 2015MkutmonNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ATMGeneProductENSBTAG00000003111 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000149311
DDX1GeneProductENSBTAG00000009906 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000079785
DGCR8GeneProductENSBTAG00000019869 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000128191
DROSHAGeneProductENSBTAG00000017551 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000113360
MRE11AGeneProductENSBTAG00000008925 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000020922
NBNGeneProductENSBTAG00000013225 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000104320
RAD50GeneProductENSBTAG00000011252 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000113522

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