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Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells
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 hav...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075040/ https://www.ncbi.nlm.nih.gov/pubmed/29950491 http://dx.doi.org/10.1101/gad.315804.118 |
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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. |
author_facet | 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. |
author_sort | Hunter, Ryan W. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6075040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60750402019-01-01 Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells 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. Genes Dev Research Communication 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. Cold Spring Harbor Laboratory Press 2018-07-01 /pmc/articles/PMC6075040/ /pubmed/29950491 http://dx.doi.org/10.1101/gad.315804.118 Text en © 2018 Hunter et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Communication 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. Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells |
title | Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells |
title_full | Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells |
title_fullStr | Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells |
title_full_unstemmed | Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells |
title_short | Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells |
title_sort | loss of dis3l2 partially phenocopies perlman syndrome in mice and results in up-regulation of igf2 in nephron progenitor cells |
topic | Research Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075040/ https://www.ncbi.nlm.nih.gov/pubmed/29950491 http://dx.doi.org/10.1101/gad.315804.118 |
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