
浏览全部资源
扫码关注微信
1.重庆医科大学附属第一医院肿瘤科,重庆 400016
2.重庆医科大学附属第一医院心血管内科,重庆 400016
李辰皓,Email:lichenhao0105@163.com,研究方向:结直肠癌发病机制。
朱宇熹,Email:zhuyuxi@hospital.cqmu.edu.cn。
收稿:2024-10-31,
修回:2024-11-20,
录用:2024-11-22,
纸质出版:2024-12-28
移动端阅览
李辰皓,游舒云,王雪莲,等.USP53在结直癌中的抗肿瘤作用及其预后价值的研究[J].重庆医科大学学报,2024,49(12):1577-1587.
Li Chenhao,You Shuyun,Wang Xuelian,et al.Anti-tumor effect and prognostic value of ubiquitin-specific protease 53 in colorectal cancer[J].Journal of Chongqing Medical University,2024,49(12):1577-1587.
李辰皓,游舒云,王雪莲,等.USP53在结直癌中的抗肿瘤作用及其预后价值的研究[J].重庆医科大学学报,2024,49(12):1577-1587. DOI: 10.13406/j.cnki.cyxb.003681.
Li Chenhao,You Shuyun,Wang Xuelian,et al.Anti-tumor effect and prognostic value of ubiquitin-specific protease 53 in colorectal cancer[J].Journal of Chongqing Medical University,2024,49(12):1577-1587. DOI: 10.13406/j.cnki.cyxb.003681.
目的
2
泛素特异性蛋白酶53(ubiquitin-specific protease 53,USP53)在结直肠癌(colon adenocarcinoma,COAD)中的临床意义和潜在机制尚不清楚。本研究采用生物信息学结合体外细胞学实验,观察USP53对结直肠癌细胞的抗癌作用。
方法
2
分析来自TCGA-COAD和GEO数据库(GSE39582数据集)的USP53表达数据。通过KEGG、GO和GSEA富集分析,探讨USP53可能参与的生物过程和信号通路。通过免疫浸润分析、药物敏感性分析结合CLUE平台和分子对接技术,预测潜在可用于治疗的小分子化合物。通过10种机器学习算法和101种集成组合构建预后预测模型,通过体外实验验证USP53的生物功能。
结果
2
USP53在COAD中具有抗肿瘤作用,低表达与较差的预后相关(
P
<
0.05)。免疫浸润分析显示USP53低表达组有更高的免疫浸润水平,以及更高的TIDE和功能障碍评分(
P
<
0.01)。体外实验表明,USP53过表达抑制了肿瘤细胞的增殖和迁移(
P
<
0.05),并抑制了上皮-间质转化(epithelial-mesenchymal transition,EMT)。
结论
2
USP53通过影响EMT、凋亡、细胞周期调控和肿瘤免疫逃逸等机制发挥抗肿瘤作用,可能成为COAD的新型预后标志物。
Objective
2
To investigate the antitumor effect of ubiquitin-specific protease 53(USP53) in colon adenocarcinoma(COAD) cells using bioinformatics methods combined with
in vitro
cellular experiments,since the clinical significance and potential mechanisms of USP53 in COAD remains unclear.
Methods
2
The expression data of USP53 from TCGA-COAD and GEO database (GSE39582 cohort) were analyzed,and KEGG,GO,and GSEA enrichment analyses were used to explore the biological processes and signaling pathways in which USP53 might be involved. The immune infiltration analysis and drug sensitivity analysis,along with the CLUE platform and molecular docking techniques,were used to predict the potential small-molecule compounds for treatment. A prognostic prediction model was established using 10 machine learning algorithms and 101 ensemble combinations,and
in vitro
experiments were performed to validate the function of USP53.
Results
2
USP53 exhibited an antitumor effect in COAD,and the low expression of USP53 was associated with poor prognosis(
P
<
0.05). The immune infiltration analysis showed that the low USP53 expression group had a higher level of immune infiltration,as well as higher TIDE and dysfunction scores(
P
<
0.01).
In vitro
experiments showed that
USP53 overexpression inhibited the proliferation and migration of tumor cells and inhibited epithelial-mesenchymal transition (EMT)(
P
<
0.05).
Conclusion
2
USP53 exerts an antitumor effect by influencing the mechanisms such as EMT,apoptosis,cell cycle regulation,and tumor immune escape,and it may become a novel prognostic marker for COAD.
Sung H , Ferlay J , Siegel RL , et al . Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 .
Center MM , Jemal A , Smith RA , et al . Worldwide variations in colorectal cancer [J ] . CA Cancer J Clin , 2009 , 59 ( 6 ): 366 - 378 .
Dekker E , Tanis PJ , Vleugels JLA , et al . Colorectal cancer [J ] . Lancet , 2019 , 394 ( 10207 ): 1467 - 1480 .
Arnold M , Sierra MS , Laversanne M , et al . Global patterns and trends in colorectal cancer incidence and mortality [J ] . Gut , 2017 , 66 ( 4 ): 683 - 691 .
Rex DK , Boland CR , Dominitz JA , et al . Colorectal cancer screening:recommendations for physicians and patients from the U. S. multi-society task force on colorectal cancer [J ] . Am J Gastroenterol , 2017 , 112 ( 7 ): 1016 - 1030 .
Li B , Qi ZP , He DL , et al . NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer [J ] . J Exp Clin Cancer Res , 2021 , 40 ( 1 ): 126 .
Yu SY , Zang WC , Qiu YC , et al . Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis [J ] . Oncogene , 2022 , 41 ( 1 ): 46 - 56 .
Vij M , Sankaranarayanan S . Biallelic mutations in ubiquitin-specific peptidase 53(USP53) causing progressive intrahepatic cholestasis. report of a case with review of literature [J ] . Pediatr Dev Pathol , 2022 , 25 ( 2 ): 207 - 212 .
Ateş BB , Ceylan AC , Hızal G , et al . A novel homozygous mutation in the USP53 gene as the cause of benign recurrent intrahepatic cholestasis in children:a case report [J ] . Turk J Pediatr , 2023 , 65 ( 6 ): 1012 - 1017 .
Kazmierczak M , Harris SL , Kazmierczak P , et al . Progressive hearing loss in mice carrying a mutation in Usp53 [J ] . J Neurosci , 2015 , 35 ( 47 ): 15582 - 15598 .
Baek D , Park KH , Lee KM , et al . Ubiquitin-specific protease 53 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells [J ] . Cell Death Dis , 2021 , 12 ( 3 ): 238 .
Liu Y , Tang W , Yao F . USP53 exerts tumor-promoting effects in triple-negative breast cancer by deubiquitinating CRKL [J ] . Cancers , 2023 , 15 ( 20 ): 5033 .
Yao Y , Ma WJ , Guo YH , et al . USP53 plays an antitumor role in hepatocellular carcinoma through deubiquitination of cytochrome C [J ] . Oncogenesis , 2022 , 11 ( 1 ): 31 .
Ritchie ME , Phipson B , Wu D , et al . Limma powers differential expression analyses for RNA-sequencing and microarray studies [J ] . Nucleic Acids Res , 2015 , 43 ( 7 ): e47 .
Wu TZ , Hu EQ , Xu SB , et al . clusterProfiler 4.0:a universal enrichment tool for interpreting omics data [J ] . Innovation(Camb) , 2021 , 2 ( 3 ): 100141 .
Yoshihara K , Shahmoradgoli M , Martínez E , et al . Inferring tumour purity and stromal and immune cell admixture from expression data [J ] . Nat Commun , 2013 , 4 : 2612 .
Hänzelmann S , Castelo R , Guinney J . GSVA:gene set variation analysis for microarray and RNA-seq data [J ] . BMC Bioinformatics , 2013 , 14 : 7 .
Bindea G , Mlecnik B , Tosolini M , et al . Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer [J ] . Immunity , 2013 , 39 ( 4 ): 782 - 795 .
Jiang P , Gu SQ , Pan D , et al . Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response [J ] . Nat Med , 2018 , 24 ( 10 ): 1550 - 1558 .
Liu ZQ , Liu L , Weng SY , et al . Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer [J ] . Nat Commun , 2022 , 13 ( 1 ): 816 .
Gui DW , Dong ZF , Peng W , et al . Ubiquitin-specific peptidase 53 inhibits the occurrence and development of clear cell renal cell carcinoma through NF-κB pathway inactivation [J ] . Cancer Med , 2021 , 10 ( 11 ): 3674 - 3688 .
Cheng W , Tang Y , Tong XB , et al . USP53 activated by H3K27 acetylation regulates cell viability,apoptosis and metabolism in esophageal carcinoma via the AMPK signaling pathway [J ] . Carcinogenesis , 2022 , 43 ( 4 ): 349 - 359 .
Tang SB , Yuan XH , Song JT , et al . Association analyses of the JAK/STAT signaling pathway with the progression and prognosis of colon cancer [J ] . Oncol Lett , 2019 , 17 ( 1 ): 159 - 164 .
Evan GI , Vousden KH . Proliferation,cell cycle and apoptosis in cancer [J ] . Nature , 2001 , 411 ( 6835 ): 342 - 348 .
Chipumuro E , Henriksen M . The ubiquitin hydrolase,USP22 contributes to 3’-end processing of JAK-STAT inducible genes [J ] . Epigenetics Chromatin , 2013 , 6 ( Suppl 1 ): P27 .
Dunn GP , Old LJ , Schreiber RD . The three Es of cancer immunoediting [J ] . Annu Rev Immunol , 2004 , 22 : 329 - 360 .
Gajewski TF , Schreiber H , Fu YX . Innate and adaptive immune cells in the tumor microenvironment [J ] . Nat Immunol , 2013 , 14 ( 10 ): 1014 - 1022 .
Creighton CJ , Gibbons DL , Kurie JM . The role of epithelial-mesenchymal transition programming in invasion and metastasis:a clinical perspective [J ] . Cancer Manag Res , 2013 , 5 : 187 - 195 .
Chanda AY , Sarkar A , Bonni S . The SUMO system and TGFβ signaling interplay in regulation of epithelial-mesenchymal transition:implications for cancer progression [J ] . Cancers , 2018 , 10 ( 8 ): 264 .
Tamaki T , Shimizu T , Niki M , et al . Immunohistochemical analysis of NANOG expression and epithelial-mesenchymal transition in pulmonary sarcomatoid carcinoma [J ] . Oncol Lett , 2017 , 13 ( 5 ): 3695 - 3702 .
Sisto M , Ribatti D , Lisi S . Cadherin signaling in cancer and autoimmune diseases [J ] . Int J Mol Sci , 2021 , 22 ( 24 ): 13358 .
0
浏览量
10
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621