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

Y. C. Wang, S. A. Wang, P. H. Chen, T. I. Hsu, W. B. Yang, Y. P. Chuang, W. C. Su, H. J. Liaw, W. C. Chang, J. J. Hung

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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.

Original languageEnglish
Pages (from-to)3669-3680
Number of pages12
JournalOncogene
Volume35
Issue number28
DOIs
Publication statusPublished - Jul 14 2016

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ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Wang, Y. C., Wang, S. A., Chen, P. H., Hsu, T. I., Yang, W. B., Chuang, Y. P., Su, W. C., Liaw, H. J., Chang, W. C., & Hung, J. J. (2016). Variants of ubiquitin-specific peptidase 24 play a crucial role in lung cancer malignancy. Oncogene, 35(28), 3669-3680. https://doi.org/10.1038/onc.2015.432