Bulk and single cells transcriptomes with experimental validation identify USP18 as a novel glioma prognosis and proliferation indicator
- Authors:
- Yang Chen
- Ren Li
- Ziao Li
- Biao Yang
- Jianhang He
- Jiayu Li
- Peize Li
- Zihan Zhou
- Yongqiang Wu
- Yuanli Zhao
- Geng Guo
-
Affiliations: Department of Neurosurgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Emergency, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China - Published online on: March 26, 2024 https://doi.org/10.3892/etm.2024.12517
- Article Number: 229
-
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
 |
 |
 |
 |
 |
|
Goodenberger ML and Jenkins RB: Genetics of adult glioma. Cancer Genet. 205:613–621. 2012.PubMed/NCBI View Article : Google Scholar | |
|
WHO Classification of Tumours Editorial Board. World Health Organization classification of tumours of the central nervous system. 5th edition. Lyon: International Agency for Research on Cancer, 2021. | |
|
Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019. Neuro Oncol. 24 (Suppl 5):v1–v95. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Ohgaki H and Kleihues P: Epidemiology and etiology of gliomas. Acta Neuropathol. 109:93–108. 2005.PubMed/NCBI View Article : Google Scholar | |
|
Verhaak RGW, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, et al: Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 17:98–110. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Lee E, Yong RL, Paddison P and Zhu J: Comparison of glioblastoma (GBM) molecular classification methods. Semin Cancer Biol. 53:201–211. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Basters A, Knobeloch KP and Fritz G: USP18-a multifunctional component in the interferon response. Biosci Rep. 38(BSR20180250)2018.PubMed/NCBI View Article : Google Scholar | |
|
Liu LQ, Ilaria R Jr, Kingsley PD, Iwama A, van Etten RA, Palis J and Zhang DE: A novel ubiquitin-specific protease, UBP43, cloned from leukemia fusion protein AML1-ETO-expressing mice, functions in hematopoietic cell differentiation. Mol Cell Biol. 19:3029–3038. 1999.PubMed/NCBI View Article : Google Scholar | |
|
Zhang X, Shin J, Molitor TW, Schook LB and Rutherford MS: Molecular responses of macrophages to porcine reproductive and respiratory syndrome virus infection. Virology. 262:152–162. 1999.PubMed/NCBI View Article : Google Scholar | |
|
Kang D, Jiang H, Wu Q, Pestka S and Fisher PB: Cloning and characterization of human ubiquitin-processing protease-43 from terminally differentiated human melanoma cells using a rapid subtraction hybridization protocol RaSH. Gene. 267:233–242. 2001.PubMed/NCBI View Article : Google Scholar | |
|
Malakhov MP, Malakhova OA, Kim KI, Ritchie KJ and Zhang DE: UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J Biol Chem. 277:9976–9981. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, Peterson LF, Shuai K and Zhang DE: Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev. 17:455–560. 2003.PubMed/NCBI View Article : Google Scholar | |
|
Malakhova OA, Kim KI, Luo J-K, Zou W, Kumar KGS, Fuchs SY, Shuai K and Zhang DE: UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J. 25:2358–2367. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Arimoto KI, Miyauchi S, Troutman TD, Zhang Y, Liu M, Stoner SA, Davis AG, Fan JB, Huang YJ, Yan M, et al: Expansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis. Nat Commun. 14(251)2023.PubMed/NCBI View Article : Google Scholar | |
|
Cai X, Feng S, Zhang J, Qiu W, Qian M and Wang Y: USP18 deubiquitinates and stabilizes Twist1 to promote epithelial-mesenchymal transition in glioblastoma cells. Am J Cancer Res. 10:1156–1169. 2020.PubMed/NCBI | |
|
Vivian J, Rao AA, Nothaft FA, Ketchum C, Armstrong J, Novak A, Pfeil J, Narkizian J, Deran AD, Musselman-Brown A, et al: Toil enables reproducible, open source, big biomedical data analyses. Nat Biotechnol. 35:314–316. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Charoentong P, Finotello F, Angelova M, Mayer C, Efremova M, Rieder D, Hackl H and Trajanoski Z: Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18:248–262. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, Morozova O, Newton Y, Radenbaugh A, Pagnotta SM, et al: Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell. 164:550–563. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Wang L, Babikir H, Müller S, Yagnik G, Shamardani K, Catalan F, Kohanbash G, Alvarado B, Di Lullo E, Kriegstein A, et al: The phenotypes of proliferating glioblastoma cells reside on a single axis of variation. Cancer Discov. 9:1708–1719. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Sun D, Wang J, Han Y, Dong X, Ge J, Zheng R, Shi X, Wang B, Li Z, Ren P, et al: TISCH: A comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res. 49 (D1):D1420–D1430. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Butler A, Hoffman P, Smibert P, Papalexi E and Satija R: Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 36:411–420. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Yu G, Wang LG, Han Y and He QY: clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 16:284–287. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Liu J, Lichtenberg T, Hoadley KA, Poisson LM, Lazar AJ, Cherniack AD, Kovatich AJ, Benz CC, Levine DA, Lee AV, et al: An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell. 173:400–416.e11. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Hänzelmann S, Castelo R and Guinney J: GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 14(7)2013.PubMed/NCBI View Article : Google Scholar | |
|
Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A, et al: Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 39:782–795. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, Treviño V, Shen H, Laird PW, Levine DA, et al: Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 4(2612)2013.PubMed/NCBI View Article : Google Scholar | |
|
Kanehisa M and Goto S: KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000.PubMed/NCBI View Article : Google Scholar | |
|
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005.PubMed/NCBI View Article : Google Scholar | |
|
Gene Ontology Consortium. Gene ontology consortium: Going forward. Nucleic Acids Res. 43 (Database Issue):D1049–D1056. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Li R, Wang YY, Wang SL, Li XP, Chen Y, Li ZA, He JH, Zhou ZH, Li JY, Guo XL, et al: GBP2 as a potential prognostic predictor with immune-related characteristics in glioma. Front Genet. 13(956632)2022.PubMed/NCBI View Article : Google Scholar | |
|
Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar | |
|
Ren Y, Yang B, Guo G, Zhang J, Sun Y, Liu D, Guo S, Wu Y, Wang X, Wang S, et al: GBP2 facilitates the progression of glioma via regulation of KIF22/EGFR signaling. Cell Death Discov. 8(208)2022.PubMed/NCBI View Article : Google Scholar | |
|
Sun Q, Li J, Wang R, Sun T, Zong Y, Wang C, Liu Y, Li X, Song Y and Zhang Y: Coxsackievirus A6 infection causes neurogenic pathogenesis in a neonatal murine model. Viruses 15: 511, 223. | |
|
Selinger M, Věchtová P, Tykalová H, Ošlejšková P, Rumlová M, Štěrba J and Grubhoffer L: Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors. Comput Struct Biotechnol J. 20:2759–2777. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Ritchie KJ, Hahn CS, Kim KI, Yan M, Rosario D, Li L, de la Torre JC and Zhang DE: Role of ISG15 protease UBP43 (USP18) in innate immunity to viral infection. Nat Med. 10:1374–1378. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Hong B, Li H, Lu Y, Zhang M, Zheng Y, Qian J and Yi Q: USP18 is crucial for IFN-γ-mediated inhibition of B16 melanoma tumorigenesis and antitumor immunity. Mol Cancer. 13(132)2014.PubMed/NCBI View Article : Google Scholar | |
|
Mustachio LM, Kawakami M, Lu Y, Rodriguez-Canales J, Mino B, Behrens C, Wistuba I, Bota-Rabassedas N, Yu J, Lee JJ, et al: The ISG15-specific protease USP18 regulates stability of PTEN. Oncotarget. 8:3–14. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Tan Y, Zhou G, Wang X, Chen W and Gao H: USP18 promotes breast cancer growth by upregulating EGFR and activating the AKT/Skp2 pathway. Int J Oncol. 53:371–383. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Tong HV, Hoan NX, Binh MT, Quyen DT, Meyer CG, Hang DTT, Hang DTD, Son HA, Van Luong H, Thuan ND, et al: Upregulation of Enzymes involved in ISGylation and ubiquitination in patients with hepatocellular carcinoma. Int J Med Sci. 17:347–353. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C, Volpi S, Li Z, Sanal O, Mansouri D, et al: Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature. 517:89–93. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Liu X, Li H, Zhong B, Blonska M, Gorjestani S, Yan M, Tian Q, Zhang DE, Lin X and Dong C: USP18 inhibits NF-κB and NFAT activation during Th17 differentiation by deubiquitinating the TAK1-TAB1 complex. J Exp Med. 210:1575–1590. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Zheng C, Zheng Z, Zhang Z, Meng J, Liu Y, Ke X, Hu Q and Wang H: IFIT5 positively regulates NF-κB signaling through synergizing the recruitment of IκB kinase (IKK) to TGF-β-activated kinase 1 (TAK1). Cell Signal. 27:2343–2354. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Numajiri Haruki A, Naito T, Nishie T, Saito S and Nagata K: Interferon-inducible antiviral protein MxA enhances cell death triggered by endoplasmic reticulum stress. J Interferon Cytokine Res. 31:847–856. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Arimoto KI, Löchte S, Stoner SA, Burkart C, Zhang Y, Miyauchi S, Wilmes S, Fan JB, Heinisch JJ, Li Z, et al: STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling. Nat Struct Mol Biol. 24:279–289. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Molinaro AM, Taylor JW, Wiencke JK and Wrensch MR: Genetic and molecular epidemiology of adult diffuse glioma. Nat Rev Neurol. 15:405–417. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Nicholson JG and Fine HA: Diffuse glioma heterogeneity and its therapeutic implications. Cancer Discov. 11:575–590. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Hernández A, Domènech M, Muñoz-Mármol AM, Carrato C and Balana C: Glioblastoma: Relationship between metabolism and immunosuppressive microenvironment. Cells. 10(3529)2021.PubMed/NCBI View Article : Google Scholar | |
|
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, et al: Structural and functional features of central nervous system lymphatic vessels. Nature. 523:337–341. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Quail DF and Joyce JA: The microenvironmental landscape of brain tumors. Cancer Cell. 31:326–341. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Sprooten J, Agostinis P and Garg AD: Type I interferons and dendritic cells in cancer immunotherapy. Int Rev Cell Mol Biol. 348:217–262. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Pyfferoen L, Brabants E, Everaert C, De Cabooter N, Heyns K, Deswarte K, Vanheerswynghels M, De Prijck S, Waegemans G, Dullaers M, et al: The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome. Oncoimmunology. 6(e1253655)2016.PubMed/NCBI View Article : Google Scholar | |
|
Chen Z, Feng X, Herting CJ, Garcia VA, Nie K, Pong WW, Rasmussen R, Dwivedi B, Seby S, Wolf SA, et al: Cellular and molecular identity of tumor-associated macrophages in glioblastoma. Cancer Res. 77:2266–228. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Dapash M, Hou D, Castro B, Lee-Chang C and Lesniak MS: The interplay between glioblastoma and its microenvironment. Cells. 10(2257)2021.PubMed/NCBI View Article : Google Scholar | |
|
Wu L and Zhang XHF: Tumor-associated neutrophils and macrophages-heterogenous but not chaotic. Front Immunol. 11(553967)2020.PubMed/NCBI View Article : Google Scholar | |
|
Broekman ML, Maas SLN, Abels ER, Mempel TR, Krichevsky AM and Breakefield XO: Multidimensional communication in the microenvirons of glioblastoma. Nat Rev Neurol. 14:482–495. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Blanchett S, Boal-Carvalho I, Layzell S and Seddon B: NF-κB and extrinsic cell death pathways-entwined do-or-die decisions for T cells. Trends Immunol. 42:76–88. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Kim CH: FOXP3 and its role in the immune system. Adv Exp Med Biol. 665:17–29. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Lu L, Barbi J and Pan F: The regulation of immune tolerance by FOXP3. Nat Rev Immunol. 17:703–717. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Yang Z, Xian H, Hu J, Tian S, Qin Y, Wang RF and Cui J: USP18 negatively regulates NF-κB signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms. Sci Rep. 5(12738)2015.PubMed/NCBI View Article : Google Scholar | |
|
Cui P, Wei F, Hou J, Su Y, Wang J and Wang S: STAT3 inhibition induced temozolomide-resistant glioblastoma apoptosis via triggering mitochondrial STAT3 translocation and respiratory chain dysfunction. Cell Signal. 71(109598)2020.PubMed/NCBI View Article : Google Scholar | |
|
Schneider WM, Chevillotte MD and Rice CM: Interferon-stimulated genes: A complex web of host defenses. Annu Rev Immunol. 32:513–545. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Bracci L, Sistigu A, Proietti E and Moschella F: The added value of type I interferons to cytotoxic treatments of cancer. Cytokine Growth Factor Rev. 36:89–97. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Parker BS, Rautela J and Hertzog PJ: Antitumour actions of interferons: Implications for cancer therapy. Nat Rev Cancer. 16:131–144. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Zitvogel L, Galluzzi L, Kepp O, Smyth MJ and Kroemer G: Type I interferons in anticancer immunity. Nat Rev Immunol. 15:405–414. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, et al: Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev. 21:2683–2710. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Stewart LA: Chemotherapy in adult high-grade glioma: A systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 359:1011–1018. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Yung WK, Prados M, Levin VA, Fetell MR, Bennett J, Mahaley MS, Salcman M and Etcubanas E: Intravenous recombinant interferon beta in patients with recurrent malignant gliomas: A phase I/II study. J Clin Oncol. 9:1945–1949. 1991.PubMed/NCBI View Article : Google Scholar | |
|
Fine HA, Wen PY, Robertson M, O'Neill A, Kowal J, Loeffler JS and Black PM: A phase I trial of a new recombinant human beta-interferon (BG9015) for the treatment of patients with recurrent gliomas. Clin Cancer Res. 3:381–387. 1997.PubMed/NCBI | |
|
Manini I, Sgorbissa A, Potu H, Tomasella A and Brancolini C: The DeISGylase USP18 limits TRAIL-induced apoptosis through the regulation of TRAIL levels: Cellular levels of TRAIL influences responsiveness to TRAIL-induced apoptosis. Cancer Biol Ther. 14:1158–1166. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Dimberg LY, Anderson CK, Camidge R, Behbakht K, Thorburn A and Ford HL: On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics. Oncogene. 32:1341–1350. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Potu H, Sgorbissa A and Brancolini C: Identification of USP18 as an important regulator of the susceptibility to IFN-alpha and drug-induced apoptosis. Cancer Res. 70:655–665. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Sgorbissa A, Tomasella A, Potu H, Manini I and Brancolini C: Type I IFNs signaling and apoptosis resistance in glioblastoma cells. Apoptosis. 16:1229–1244. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Zong H, Verhaak RGW and Canoll P: The cellular origin for malignant glioma and prospects for clinical advancements. Expert Rev Mol Diagn. 12:383–394. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Omuro A and DeAngelis LM: Glioblastoma and other malignant gliomas: A clinical review. JAMA. 310:1842–1850. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Nieto MA, Huang RYJ, Jackson RA and Thiery JP: EMT: 2016. Cell. 166:21–45. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Nieto MA: Epithelial-mesenchymal transitions in development and disease: Old views and new perspectives. Int J Dev Biol. 53:1541–1547. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Noronha C, Ribeiro AS, Taipa R, Castro DS, Reis J, Faria C and Paredes J: Cadherin expression and EMT: A focus on gliomas. Biomedicines. 9(1328)2021.PubMed/NCBI View Article : Google Scholar | |
|
Li L, Yin Y, Zhang J, Wu X, Liu J, Chai J, Yang Y, Li M, Jia Q and Liu Y: USP18 regulates the malignant phenotypes of glioblastoma stem cells. Pathol Res Pract. 247(154572)2023.PubMed/NCBI View Article : Google Scholar |
