Abstract
Loss of function of the DIS3L2 exoribonuclease is associated with Wilms tumor and the Perlman congenital overgrowth syndrome. LIN28, a Wilms tumor oncoprotein, triggers the DIS3L2-mediated degradation of the precursor of let-7, a microRNA that inhibits Wilms tumor development. These observations have led to speculation that DIS3L2-mediated tumor suppression is attributable to let-7 regulation. Here we examine new DIS3L2-deficient cell lines and mouse models, demonstrating that DIS3L2 loss has no effect on mature let-7 levels. Rather, analysis of Dis3l2-null nephron progenitor cells, a potential cell of origin of Wilms tumors, reveals up-regulation of Igf2, a growth-promoting gene strongly associated with Wilms tumorigenesis. These findings nominate a new potential mechanism underlying the pathology associated with DIS3L2 deficiency.
Original language | English (US) |
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Pages (from-to) | 903-908 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 32 |
Issue number | 13-14 |
DOIs | |
State | Published - Jul 1 2018 |
Keywords
- DIS3L2
- Igf2
- LIN28
- Let-7
- MicroRNA
- Perlman syndrome
- Wilms tumor
ASJC Scopus subject areas
- General Medicine