Abstract:
:Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Urbach A,Yermalovich A,Zhang J,Spina CS,Zhu H,Perez-Atayde AR,Shukrun R,Charlton J,Sebire N,Mifsud W,Dekel B,Pritchard-Jones K,Daley GQdoi
10.1101/gad.237149.113subject
Has Abstractpub_date
2014-05-01 00:00:00pages
971-82issue
9eissn
0890-9369issn
1549-5477pii
gad.237149.113journal_volume
28pub_type
杂志文章abstract::Pre-mRNA processing is coupled with transcription. It is still unclear if the transcription machinery can also directly affect the cytoplasmic fate of a transcript, such as its intracellular localization. In yeast, the RNA-binding protein She2p binds several mRNAs and targets them for localization at the bud. Here we ...
journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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