Loss of Dis3l2 partially phenocopies perlman syndrome in mice and results in upregulation of Igf2 in nephron progenitor cells

Ryan W. Hunter, Yangjian Liu, Hema Manjunath, Asha Acharya, Benjamin T. Jones, He Zhang, Beibei Chen, Harini Ramalingam, Robert E Hammer, Yang Xie, James A Richardson, Dinesh Rakheja, Thomas J Carroll, Joshua T Mendell

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)903-908
Number of pages6
JournalGenes and Development
Volume32
Issue number13-14
DOIs
StatePublished - Jul 1 2018

Fingerprint

Wilms Tumor
Nephrons
Up-Regulation
Stem Cells
Exoribonucleases
Oncogene Proteins
MicroRNAs
Carcinogenesis
Pathology
Cell Line
Nephroblastomatosis, Fetal Ascites, Macrosomia, And Wilms Tumor
Growth
Genes
Neoplasms

Keywords

  • DIS3L2
  • Igf2
  • Let-7
  • LIN28
  • MicroRNA
  • Perlman syndrome
  • Wilms tumor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Loss of Dis3l2 partially phenocopies perlman syndrome in mice and results in upregulation 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.

In: Genes and Development, Vol. 32, No. 13-14, 01.07.2018, p. 903-908.

Research output: Contribution to journalArticle

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 upregulation of Igf2 in nephron progenitor cells. In: Genes and Development. 2018 ; Vol. 32, No. 13-14. pp. 903-908.
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