Author:
Hunter Ryan W.,Liu Yangjian,Manjunath Hema,Acharya Asha,Jones Benjamin T.,Zhang He,Chen Beibei,Ramalingam Harini,Hammer Robert E.,Xie Yang,Richardson James A.,Rakheja Dinesh,Carroll Thomas J.,Mendell Joshua T.
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.
Funder
Cancer Prevention Research Institute of Texas
National Institutes of Health
Welch Foundation
University of Texas Southwestern Center for Regenerative Science and Medicine
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
34 articles.
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