Mutations in MicroRNA Processing Genes in Wilms Tumors Derepress the Regulator

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2018 Jul 21

PMID 30026293

Citations 24

Authors

Kenneth S 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

Affiliations

Soon will be listed here.

Abstract

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 ) is a microRNA target gene that is overexpressed in Wilms tumors with mutations in microRNA processing genes. Wilms tumors can also overexpress through copy number alterations, and expression correlates with prognosis in Wilms tumors. overexpression accelerates growth of Wilms tumor cells in vitro and induces neoplastic growth in the developing mouse kidney in vivo. In both settings, transactivates (), 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.

Citing Articles

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The Role of PLAG1 in Mouse Brain Development and Neurogenesis.

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