5 Citations (Scopus)

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    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