Mutations in microRNA processing genes in wilms tumors derepress the IGF2 regulator PLAG1

Kenneth Chen, Emily K. Stroup, Albert Budhipramono, Dinesh Rakheja, Diana Nichols-Vinueza, Lin Xu, Sarai H. Stuart, Abhay A. Shukla, Claudette Fraire, Joshua T Mendell, James F Amatruda

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Many childhood Wilms tumors are driven by mutations in the microRNA biogenesis machinery, but the mechanism by which these mutations drive tumorigenesis is unknown. Here we show that the transcription factor pleomorphic adenoma gene 1 (PLAG1) is a microRNA target gene that is overexpressed in Wilms tumors with mutations in microRNA processing genes. Wilms tumors can also overexpress PLAG1 through copy number alterations, and PLAG1 expression correlates with prognosis in Wilms tumors. PLAG1 overexpression accelerates growth of Wilms tumor cells in vitro and induces neoplastic growth in the developing mouse kidney in vivo. In both settings, PLAG1 transactivates insulin-like growth factor 2 (IGF2), a key Wilms tumor oncogene, and drives mammalian target of rapamycin complex 1 (mTORC1) signaling. These data link microRNA impairment to the PLAG1–IGF2 pathway, providing new insight into the manner in which common Wilms tumor mutations drive disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)996-1007
Number of pages12
JournalGenes and Development
Issue number15-16
StatePublished - Aug 1 2018


  • IGF2
  • Kidney
  • PLAG1
  • Pediatric cancer
  • Wilms tumor
  • nicroRNA processing

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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