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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Hepatocellular Carcinoma | Research

High USP32 expression contributes to cancer progression and is correlated with immune infiltrates in hepatocellular carcinoma

Authors: Mengxi Xiu, Wenfang Bao, Jialin Wang, Jingde Chen, Yandong Li, Yanan Hai

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Ubiquitin-specific protease 32 (USP32) is a highly conserved gene that promotes cancer progression. However, its role in hepatocellular carcinoma (HCC) is not well understood. The aim of this project is to explore the clinical significance and functions of USP32 in HCC.

Methods

The expression of USP32 in HCC was evaluated using data from TCGA, GEO, TISCH, tissue microarray, and human HCC samples from our hospital. Survival analysis, PPI analysis and GSEA analysis were performed to evaluate USP32-related clinical significance, key molecules and enrichment pathways. Using the ssGSEA algorithm and TIMER, we investigated the relationships between USP32 and immune infiltrates in the TME. Univariate and multivariate Cox regression analyses were then used to identify key USP32-related immunomodulators and constructed a USP32-related immune prognostic model. Finally, CCK8, transwell and colony formation assays of HCC cells were performed and an HCC nude mouse model was established to verify the oncogenic role of USP32.

Results

USP32 is overexpressed in HCC and its expression is an independent predictive factor for outcomes of HCC patients. USP32 is associated with pathways related to cell behaviors and cancer signaling, and its expression is significantly correlated with the infiltration of immune cells in the TME. We also successfully constructed a USP32-related immune prognostic model using 5 genes. Wet experiments confirmed that knockdown of USP32 could repress the proliferation, colony formation and migration of HCC cells in vitro and inhibit tumor growth in vivo.

Conclusion

USP32 is highly expressed in HCC and closely correlates with the TME of HCC. It is a potential target for improving the efficacy of chemotherapy and developing new strategies for targeted therapy and immunotherapy in HCC.
Appendix
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Literature
1.
Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet (London England). 2022;400(10360):1345–62.PubMedCrossRef
2.
Llovet JM, Montal R, Sia D, Finn RS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Reviews Clin Oncol. 2018;15(10):599–616.CrossRef
3.
Rape M. Ubiquitylation at the crossroads of development and Disease. Nat Rev Mol Cell Biol. 2018;19(1):59–70.PubMedCrossRef
4.
Cruz L, Soares P, Correia M. Ubiquitin-specific proteases: players in Cancer Cellular processes. Pharmaceuticals (Basel Switzerland). 2021;14(9).
5.
6.
7.
Akhavantabasi S, Akman HB, Sapmaz A, Keller J, Petty EM, Erson AE. USP32 is an active, membrane-bound ubiquitin protease overexpressed in breast cancers. Mammalian Genome: Official Journal of the International Mammalian Genome Society. 2010;21(7–8):388–97.PubMedCrossRef
8.
Dou N, Hu Q, Li L, Wu Q, Li Y, Gao Y. USP32 promotes tumorigenesis and chemoresistance in gastric carcinoma via upregulation of SMAD2. Int J Biol Sci. 2020;16(9):1648–57.PubMedPubMedCentralCrossRef
9.
Nakae A, Kodama M, Okamoto T, Tokunaga M, Shimura H, Hashimoto K, et al. Ubiquitin specific peptidase 32 acts as an oncogene in epithelial Ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1. Biochem Biophys Res Commun. 2021;552:120–7.PubMedCrossRef
10.
Chen S, Chen X, Li Z, Mao J, Jiang W, Zhu Z, et al. Identification of ubiquitin-specific protease 32 as an oncogene in glioblastoma and the underlying mechanisms. Sci Rep. 2022;12(1):6445.PubMedPubMedCentralCrossRef
11.
Li C, Gao Z, Cui Z, Liu Z, Bian Y, Sun H et al. Deubiquitylation of Rab35 by USP32 promotes the transmission of imatinib resistance by enhancing exosome secretion in gastrointestinal stromal tumours. Oncogene. 2023.
12.
Zhang H, Tao Y, Ding X, Wang Y, Wang X. Roles of the hsa_circ_0013880/USP32/Rap1b axis in the proliferation and apoptosis of acute Myeloid Leukemia cells. Acta Biochim Biophys Sin. 2023;55(3):382–93.PubMedPubMedCentralCrossRef
13.
Andersen PK, Gill RD. Cox’s regression model for counting processes: a large sample study. The Annals of Statistics. 1982;10(4):1100–20.CrossRef
14.
Lánczky A, Győrffy B. Web-based Survival Analysis Tool tailored for Medical Research (KMplot): development and implementation. J Med Internet Res. 2021;23(7):e27633.PubMedPubMedCentralCrossRef
15.
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.PubMedPubMedCentralCrossRef
16.
Zhou J, Wan R, Tian Q, Wu Z, Lin Z, Wang W, et al. Transcriptome sequencing analysis of lncRNA and mRNA expression profiles in bone Nonunion. Oxidative Med Cell Longev. 2022;2022:9110449.CrossRef
17.
Huang R, Zheng X, Wang J. Bioinformatic exploration of the immune related molecular mechanism underlying pulmonary arterial Hypertension. Bioengineered. 2021;12(1):3137–47.PubMedPubMedCentralCrossRef
18.
Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021;49(D1):D605–d12.PubMedCrossRef
19.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef
20.
21.
22.
Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Science: A Publication of the Protein Society. 2019;28(11):1947–51.CrossRef
23.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–d92.PubMedCrossRef
24.
Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7.PubMedCentralCrossRef
25.
Sun D, Wang J, Han Y, Dong X, Ge J, Zheng R, et al. TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of Tumor microenvironment. Nucleic Acids Res. 2021;49(D1):D1420–d30.PubMedCrossRef
26.
Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H, Forbes S, et al. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41(Database issue):D955–61.
27.
Geeleher P, Cox N, Huang RS. pRRophetic: an R package for prediction of clinical chemotherapeutic response from Tumor gene expression levels. PLoS ONE. 2014;9(9):e107468.PubMedPubMedCentralCrossRef
28.
Hu W, Wei H, Li K, Li P, Lin J, Feng R. Downregulation of USP32 inhibits cell proliferation, migration and invasion in human small cell Lung cancer. Cell Prolif. 2017;50(4).
29.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102(43):15545–50.PubMedPubMedCentralCrossRef
30.
Marin JJG, Macias RIR, Monte MJ, Romero MR, Asensio M, Sanchez-Martin A et al. Molecular bases of Drug Resistance in Hepatocellular Carcinoma. Cancers. 2020;12(6).
31.
Pham C, Fong TL, Zhang J, Liu L. Striking Racial/Ethnic disparities in Liver Cancer incidence rates and temporal trends in California, 1988–2012. J Natl Cancer Inst. 2018;110(11):1259–69.PubMedPubMedCentralCrossRef
32.
Hoehn RS, Hanseman DJ, Wima K, Ertel AE, Paquette IM, Abbott DE, et al. Does race affect management and survival in hepatocellular carcinoma in the United States? Surgery. 2015;158(5):1244–51.PubMedCrossRef
33.
Wen GM, Song CL, Liu DH, Xia P. Different races have different immune microenvironments: comparison of White and Asian patients with Liver cancer. Am J cancer Res. 2023;13(3):1118–27.PubMedPubMedCentral
34.
Craig AJ, Garcia-Lezana T, Ruiz de Galarreta M, Villacorta-Martin C, Kozlova EG, Martins-Filho SN, et al. Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of Tumor progression in hepatocellular carcinoma. PLoS Genet. 2021;17(6):e1009589.PubMedPubMedCentralCrossRef
35.
Gu X, Mao Y, Shi C, Ye W, Hou N, Xu L, et al. MAGEC2 correlates with unfavorable prognosis and promotes Tumor Development in HCC Via epithelial-mesenchymal transition. OncoTargets and Therapy. 2019;12:7843–55.PubMedPubMedCentralCrossRef
36.
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321–30.CrossRef
37.
38.
Chen Y, Sun J, Luo Y, Liu J, Wang X, Feng R, et al. Pharmaceutical targeting Th2-mediated immunity enhances immunotherapy response in Breast cancer. J Translational Med. 2022;20(1):615.CrossRef
39.
Dees S, Ganesan R, Singh S, Grewal IS. Regulatory T cell targeting in cancer: emerging strategies in immunotherapy. Eur J Immunol. 2021;51(2):280–91.PubMedCrossRef
40.
Philip M, Schietinger A. CD8(+) T cell differentiation and dysfunction in cancer. Nat Rev Immunol. 2022;22(4):209–23.PubMedCrossRef
41.
Wang SS, Liu W, Ly D, Xu H, Qu L, Zhang L. Tumor-infiltrating B cells: their role and application in anti-tumor immunity in Lung cancer. Cell Mol Immunol. 2019;16(1):6–18.CrossRef
42.
Wagner JA, Rosario M, Romee R, Berrien-Elliott MM, Schneider SE, Leong JW, et al. CD56bright NK cells exhibit potent antitumor responses following IL-15 priming. J Clin Investig. 2017;127(11):4042–58.PubMedCentralCrossRef
43.
Bao MH, Wong CC, Hypoxia. Metabolic reprogramming, and Drug Resistance in Liver Cancer. Cells. 2021;10(7).
44.
Chandrasekaran AP, Kaushal K, Park CH, Kim KS, Ramakrishna S. USP32 confers cancer cell resistance to YM155 via promoting ER-associated degradation of solute carrier protein SLC35F2. Theranostics. 2021;11(20):9752–71.PubMedPubMedCentralCrossRef
45.
Zhou CC, Yang F, Yuan SX, Ma JZ, Liu F, Yuan JH, et al. Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma. Hepatology (Baltimore MD). 2016;63(3):850–63.CrossRef
46.
Tang W, Xue R, Weng S, Wu J, Fang Y, Wang Y, et al. BIRC6 promotes hepatocellular carcinogenesis: interaction of BIRC6 with p53 facilitating p53 degradation. Int J Cancer. 2015;136(6):E475–87.PubMedCrossRef
Metadata
Title
High USP32 expression contributes to cancer progression and is correlated with immune infiltrates in hepatocellular carcinoma
Authors
Mengxi Xiu
Wenfang Bao
Jialin Wang
Jingde Chen
Yandong Li
Yanan Hai
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11617-4

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