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Oncogene. 2016 Jul 14;35(28):3669-80. doi: 10.1038/onc.2015.432. Epub 2015 Nov 16.

Variants of ubiquitin-specific peptidase 24 play a crucial role in lung cancer malignancy.

Author information

1
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
2
Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
3
Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan.
4
Center for Infectious Disease and Signal Transduction, National Cheng Kung University, Tainan, Taiwan.
5
The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei, Taiwan.
6
Department of Internal Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
7
Department of Life Science, College of Bioscience in Biotechnology, National Cheng Kung University, Tainan, Taiwan.
8
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

Ubiquitin is a critical modifier regulating the degradation and function of its target proteins during posttranslational modification. Here we found that ubiquitin-specific peptidase 24 (USP24) is highly expressed in cell lines with enhanced malignancy and in late-stage lung cancer clinical samples. Studying single-nucleotide polymorphisms (SNPs) of USP24 using genomic DNA of lung cancer patients revealed an increase in SNP 7656C/T. When using RNA specimens instead of the genomic DNA of lung cancer patients, we found significant increases in the ratios of variants 930C/T and 7656T/C, suggesting that variants at these two sites are not only caused by the SNP of DNA but also by the RNA editing. USP24-930T and USP24-7656C increase USP24 expression levels by increasing RNA stability. Knocking down USP24 increased Suv39h1 level through a decrease in mouse double-minute 2 homolog levels, thus enhancing lysine-9 methylation of histone H3, and resulting in the prevention of lung cancer malignancy. In conclusion, as USP24 variant analysis revealed a higher ratio of variants in blood specimens of lung cancer patients than that in normal individuals, USP24-930T and USP24-7656C might be useful as diagnostic markers for cancer detection.

PMID:
26568301
DOI:
10.1038/onc.2015.432
[Indexed for MEDLINE]

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