title: Variants of ubiquitin-specific peptidase 24 play a crucial role in lung cancer malignancy.
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.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: S-A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: P-H
authors.initials: PH
authors.lastname: Chen
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.|Center for Infectious Disease and Signal Transduction, National Cheng Kung University, Tainan, Taiwan.|The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: T-I
authors.initials: TI
authors.lastname: Hsu
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: W-B
authors.initials: WB
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Chuang
authors.affiliation: Department of Internal Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: W-C
authors.initials: WC
authors.lastname: Su
authors.affiliation: Department of Life Science, College of Bioscience in Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Liaw
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: W-C
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.|Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.|Center for Infectious Disease and Signal Transduction, National Cheng Kung University, Tainan, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Hung
mesh_terms: D000072283:A549 Cells; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020871:RNA Stability / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012097:Repressor Proteins; C513810:USP24 protein, human; C407843:SUV39H1 protein, human; D008780:Methyltransferases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D043222:Ubiquitin Thiolesterase