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Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells.

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.

SUBMITTER: Hunter RW 

PROVIDER: S-EPMC6075040 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Loss of <i>Dis3l2</i> partially phenocopies Perlman syndrome in mice and results in up-regulation of <i>Igf2</i> in nephron progenitor cells.

Hunter Ryan W RW   Liu Yangjian Y   Manjunath Hema H   Acharya Asha A   Jones Benjamin T BT   Zhang He H   Chen Beibei B   Ramalingam Harini H   Hammer Robert E RE   Xie Yang Y   Richardson James A JA   Rakheja Dinesh D   Carroll Thomas J TJ   Mendell Joshua T JT  

Genes & development 20180627 13-14

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  ...[more]

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