Genetic ablation of Rbm38 promotes lymphomagenesis in the context of mutant p53 by downregulating PTEN

Jin Zhang, Enshun Xu, Cong Ren, Hee Jung Yang, Yanhong Zhang, Wenqiang Sun, Xiangmudong Kong, Weici Zhang, Mingyi Chen, Eric Huang, Xinbin Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often altered in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice by shortening lifespan, altering tumor incidence, and promoting T-cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T-cell development. Furthermore, Rbm38 was required for Pten expression via stabilization of Pten mRNA through an AU-rich element in its 3'UTR. Our results suggest that Rbm38 controls T-cell lymphomagenesis by jointly modulating mutant p53 and Pten, with possible therapeutic implications for treating T-cell malignancies. Significance: An RNA-binding protein controls T-cell lymphomagenesis by jointly modulating mutant p53 and PTEN, with possible therapeutic implications for treating T-cell malignancies.

Original languageEnglish (US)
Pages (from-to)1511-1521
Number of pages11
JournalCancer Research
Volume78
Issue number6
DOIs
StatePublished - Mar 15 2018

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Down-Regulation
T-Lymphocytes
Neoplasms
RNA-Binding Proteins
AU Rich Elements
3' Untranslated Regions
Therapeutics
Messenger RNA
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Genetic ablation of Rbm38 promotes lymphomagenesis in the context of mutant p53 by downregulating PTEN. / Zhang, Jin; Xu, Enshun; Ren, Cong; Yang, Hee Jung; Zhang, Yanhong; Sun, Wenqiang; Kong, Xiangmudong; Zhang, Weici; Chen, Mingyi; Huang, Eric; Chen, Xinbin.

In: Cancer Research, Vol. 78, No. 6, 15.03.2018, p. 1511-1521.

Research output: Contribution to journalArticle

Zhang, J, Xu, E, Ren, C, Yang, HJ, Zhang, Y, Sun, W, Kong, X, Zhang, W, Chen, M, Huang, E & Chen, X 2018, 'Genetic ablation of Rbm38 promotes lymphomagenesis in the context of mutant p53 by downregulating PTEN', Cancer Research, vol. 78, no. 6, pp. 1511-1521. https://doi.org/10.1158/0008-5472.CAN-17-2457
Zhang, Jin ; Xu, Enshun ; Ren, Cong ; Yang, Hee Jung ; Zhang, Yanhong ; Sun, Wenqiang ; Kong, Xiangmudong ; Zhang, Weici ; Chen, Mingyi ; Huang, Eric ; Chen, Xinbin. / Genetic ablation of Rbm38 promotes lymphomagenesis in the context of mutant p53 by downregulating PTEN. In: Cancer Research. 2018 ; Vol. 78, No. 6. pp. 1511-1521.
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AU - Sun, Wenqiang

AU - Kong, Xiangmudong

AU - Zhang, Weici

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