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

Yi-Ching Wang, S. A. Wang, P. H. Chen, T. I. Hsu, W. B. Yang, Y. P. Chuang, Wu-Chou Su, Hung-Jiun Liaw, W. C. Chang, Jan-Jong Hung

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7 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)3669-3680
頁數12
期刊Oncogene
35
發行號28
DOIs
出版狀態Published - 2016 七月 14

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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