Genetic Ablation of Rbm38 Promotes Lymphomagenesis in the Context of Mutant p53 by Downregulating PTEN

被引:34
作者
Zhang, Jin [1 ,2 ]
Xu, Enshun [3 ]
Ren, Cong [4 ]
Yang, Hee Jung [1 ,2 ]
Zhang, Yanhong [1 ,2 ]
Sun, Wenqiang [1 ,2 ]
Kong, Xiangmudong [1 ,2 ]
Zhang, Weici [5 ]
Chen, Mingyi [6 ]
Huang, Eric [7 ]
Chen, Xinbin [1 ,2 ]
机构
[1] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA
[2] Univ Calif Davis, Sch Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA
[3] Nanjing Agr Univ, Coll Agr, Nanjing, Jiangsu, Peoples R China
[4] Jiangnan Univ, Sch Biotechnol, Wuxi, Peoples R China
[5] Univ Calif Davis, Sch Med, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA
[6] Univ Texas Southwestern Med Ctr Dallas, Dept Pathol, Dallas, TX USA
[7] Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Davis, CA 95616 USA
关键词
RNA-BINDING PROTEIN; MESSENGER-RNA; T-CELL; TRANSCRIPTION FACTOR; TUMOR-SUPPRESSOR; TARGET GENES; RNPC1; CANCER; FAMILY; GAIN;
D O I
10.1158/0008-5472.CAN-17-2457
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:1511 / 1521
页数:11
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