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USP37的综合泛癌分析及在胰腺癌中的功能验证

An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer.

作者信息

Chen Jiafei, Lin Liang, Chen Dongxing, Wang Jingui, Zhou Wuhan

机构信息

The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China.

Department of Hepatobiliary Surgery, The First Hospital of Putian City, Chengxiang, Fujian, China.

出版信息

Front Cell Dev Biol. 2025 Aug 25;13:1659747. doi: 10.3389/fcell.2025.1659747. eCollection 2025.

DOI:10.3389/fcell.2025.1659747
PMID:40926837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12415066/
Abstract

BACKGROUND

USP37, a versatile deubiquitinase, plays a pivotal role in numerous cellular functions. Although its involvement in cancer development is well-established, the comprehensive pan-cancer analysis of USP37 remains relatively uncharted.

METHODS

RNA sequencing data from both normal and cancerous tissues were retrieved from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Genomic alterations in USP37 across multiple cancer types were examined using cBioPortal. Protein-related information on USP37 was sourced from the Human Protein Atlas (HPA) and Protein-Protein Interaction (PPI) databases. Additionally, Western blotting was conducted to evaluate USP37 expression in clinical samples and pancreatic cancer cell lines. The prognostic relevance of USP37 across various cancers was analyzed using univariate Cox regression and Kaplan-Meier survival curves. Gene Set Enrichment Analysis (GSEA) was performed to identify cancer hallmarks associated with USP37. USP37 protein levels were quantified via immunoblotting, and and functional assays were employed to assess its role in the proliferation of pancreatic cancer cells.

RESULTS

USP37 was found to be aberrantly expressed in several tumor types, with significant association with poor prognosis in certain cancers, including pancreatic cancer. Its expression was also strongly correlated with immune regulators, tumor mutational burden (TMB), and microsatellite instability (MSI), highlighting its potential as a predictive marker for immunotherapy outcomes. Functional assays demonstrated that USP37 fosters proliferation, migration, and invasion in pancreatic cancer cells, further underscoring its role as an oncogene.

CONCLUSION

USP37 holds promise as a biomarker and therapeutic target in clinical oncology, providing new insights into its function in cancer.

摘要

背景

USP37是一种多功能去泛素化酶,在众多细胞功能中发挥关键作用。尽管其参与癌症发展已得到充分证实,但对USP37的全面泛癌分析仍相对未知。

方法

从癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库中检索正常组织和癌组织的RNA测序数据。使用cBioPortal检查多种癌症类型中USP37的基因组改变。关于USP37的蛋白质相关信息来自人类蛋白质图谱(HPA)和蛋白质-蛋白质相互作用(PPI)数据库。此外,进行蛋白质印迹以评估USP37在临床样本和胰腺癌细胞系中的表达。使用单变量Cox回归和Kaplan-Meier生存曲线分析USP37在各种癌症中的预后相关性。进行基因集富集分析(GSEA)以鉴定与USP37相关的癌症特征。通过免疫印迹定量USP37蛋白水平,并采用功能测定评估其在胰腺癌细胞增殖中的作用。

结果

发现USP37在几种肿瘤类型中异常表达,与某些癌症(包括胰腺癌)的不良预后显著相关。其表达还与免疫调节因子、肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)密切相关,突出了其作为免疫治疗结果预测标志物的潜力。功能测定表明USP37促进胰腺癌细胞的增殖、迁移和侵袭,进一步强调了其作为癌基因的作用。

结论

USP37有望成为临床肿瘤学中的生物标志物和治疗靶点,为其在癌症中的功能提供新的见解。

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本文引用的文献

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USP37 counteracts HLTF to protect damaged replication forks and promote survival of BRCA1-deficient cells and PARP inhibitor resistance.USP37通过抵消HLTF来保护受损的复制叉,并促进BRCA1缺陷细胞的存活和对PARP抑制剂的抗性。
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CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer.CDK1介导的USP37磷酸化调控SND1稳定性并促进结直肠癌的肿瘤发生。
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USP37 as a novel regulator of NRF2 protein stability and chemoresistance in HCC.USP37作为肝癌中NRF2蛋白稳定性和化疗耐药性的新型调节因子。
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USP10 promotes pancreatic ductal adenocarcinoma progression by attenuating FOXC1 protein degradation to activate the WNT signaling pathway.USP10 通过减弱 FOXC1 蛋白降解来激活 WNT 信号通路,从而促进胰腺导管腺癌的进展。
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USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway.USP32通过去泛素化BAG3并激活RAF-MEK-ERK信号通路促进非小细胞肺癌进展。
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