Abstract
Human glioma is a kind of common and fatal intracranial tumor. Therefore, exploring effective drug targets for glioma is the main task of basic and clinical research. This study investigated the role of ubiquitin protein ligase E3 module N-recognition 5 (UBR5) in glioma and the underlying mechanism. First, TCGA datasets were employed to analyze the expression of UBR5 in glioblastoma or normal tissues. Western blot assay was applied to examine the protein expression level of UBR5 in glioma or adjacent tissues and other cell lines. It was found that UBR5 was highly expressed in glioma tissues and cells. Then, we discovered that UBR5 accelerated the invasion, proliferation, and migration of transfected glioma cells by colony formation, immunofluorescence staining, transwell, and wound healing assays. Furthermore, Western blot analysis revealed that UBR5 promoted the epithelial–mesenchymal transformation of glioma cells and regulated the ECRG4/NF-κB pathway. Finally, animal experiments and IHC analysis suggested that UBR5 promoted tumor growth in U251-MG cell-injected mice. In conclusion, this study found that UBR5 promoted the migration and invasion of glioma cells by regulating the ECRG4/NF-κB pathway.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12038-022-00280-9/MediaObjects/12038_2022_280_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12038-022-00280-9/MediaObjects/12038_2022_280_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12038-022-00280-9/MediaObjects/12038_2022_280_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12038-022-00280-9/MediaObjects/12038_2022_280_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12038-022-00280-9/MediaObjects/12038_2022_280_Fig5_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12038-022-00280-9/MediaObjects/12038_2022_280_Fig6_HTML.png)
Similar content being viewed by others
References
Chen L, Yuan R, Wen C, et al. 2021 E3 ubiquitin ligase UBR5 promotes pancreatic cancer growth and aerobic glycolysis by downregulating FBP1 via destabilization of C/EBPα. Oncogene 40 262–276
DiDonato JA, Mercurio F and Karin M 2012 NF-κB and the link between inflammation and cancer. Immunol. Rev. 246 379–400
Ding F, Zhu X, Song X, et al. 2020 UBR5 oncogene as an indicator of poor prognosis in gastric cancer. Exp. Ther. Med. 20 7
Ji SQ, Zhang YX and Yang BH 2017 UBR5 promotes cell proliferation and inhibits apoptosis in colon cancer by destablizing P21. Pharmazie 72 408–413
Jia J, Dai S, Sun X, et al. 2015 A preliminary study of the effect of ECRG4 overexpression on the proliferation and apoptosis of human laryngeal cancer cells and the underlying mechanisms. Mol. Med. Rep. 12 5058–5064
Leboeuf D, Abakumova T, Prikazchikova T, et al. 2020 Downregulation of the Arg/N-degron pathway sensitizes cancer cells to chemotherapy in vivo. Mol. Ther. 28 1092–1104
Li S and Ding X 2017 TRPC Channels and Glioma. Adv. Exp. Med. Biol. 976 157–165
Li W, Liu X, Zhang B, et al. 2010 Overexpression of candidate tumor suppressor ECRG4 inhibits glioma proliferation and invasion. J. Exp. Clin. Cancer Res. 29 89
Li J, Zhang W, Gao J, et al. 2021 E3 ubiquitin ligase UBR5 promotes the metastasis of pancreatic cancer via destabilizing F-actin cap** protein CAPZA1. Front. Oncol. 11 634167
Liao L, Song M, Li X, et al. 2017 E3 ubiquitin ligase UBR5 drives the growth and metastasis of triple-negative breast cancer. Cancer Res. 77 2090–2101
Peng M, Yang D, Hou Y, et al. 2019 Intracellular citrate accumulation by oxidized ATM-mediated metabolism reprogramming via PFKP and CS enhances hypoxic breast cancer cell invasion and metastasis. Cell Death Dis. 10 228
Qiao X, Liu Y, Prada ML, et al. 2020 UBR5 Is coamplified with MYC in breast tumors and encodes an ubiquitin ligase that limits myc-dependent apoptosis. Cancer Res. 80 1414–1427
Qin X and Zhang P 2019 ECRG4: a new potential target in precision medicine. Front. Med. 13 540–546
Saurabh K, Shah PP, Doll MA, Siskind LJ and Beverly LJ 2020 UBR-box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target. BMC Cancer 20 824
Shearer RF, Iconomou M, Watts CK and Saunders DN 2015 Functional roles of the E3 ubiquitin ligase UBR5 in cancer. Mol. Cancer Res. 13 1523–1532
Song M, Yeku OO, Rafiq S, et al. 2020 Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages. Nat. Commun. 11 6298
Wang J, Zhao X, ** L, Wu G and Yang Y 2017 UBR5 Contributes to colorectal cancer progression by destabilizing the tumor suppressor ECRG4. Dig. Dis. Sci. 62 2781–2789
Wang H, Zhao S, Chen B, et al. 2018 Repression of the expression of PPP3CC by ZEB1 confers activation of NF-κB and contributes to invasion and growth in glioma cells. Jpn. J. Clin. Oncol. 48 175–183
Wang Z, Kang L, Zhang H, et al. 2019 AKT drives SOX2 overexpression and cancer cell stemness in esophageal cancer by protecting SOX2 from UBR5-mediated degradation. Oncogene 38 5250–5264
World Medical Association 2013 Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 310 2191–2194
**e Z, Liang H, Wang J, et al. 2017 Significance of the E3 ubiquitin protein UBR5 as an oncogene and a prognostic biomarker in colorectal cancer. Oncotarget 8 108079–108092
Yang M, Jiang N, Cao QW, Ma MQ and Sun Q 2016 The E3 ligase UBR5 regulates gastric cancer cell growth by destabilizing the tumor suppressor GKN1. Biochem. Biophys. Res. Commun. 478 1624–1629
Yang Y, Zhao J, Mao Y, et al. 2020 UBR5 over-expression contributes to poor prognosis and tamoxifen resistance of ERa+ breast cancer by stabilizing β-catenin. Breast Cancer Res. Treat. 184 699–710
Zhang Z, Zheng X, Li J, et al. 2019 Overexpression of UBR5 promotes tumor growth in gallbladder cancer via PTEN/PI3K/Akt signal pathway. J. Cell. Biochem. https://doi.org/10.1002/jcb.28431
Zhang Y, Hou J, Shi S, et al. 2021 CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9. Cell Death Dis. 12 118
Funding
This work was supported by the Medical Science Research Project of Hebei Province (Grant No. 20190063).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors state that there are no conflicts of interest to disclose.
Ethics approval
Ethical approval was obtained from the Ethics Committee of the Second Hospital of Hebei Medical University.
Statement of Informed Consent
Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.
Contribution of authors
Qiang Wu and Ling Liu designed the study, supervised the data collection, Yan Feng analyzed the data, interpreted the data, Liqun Wang, **n Liu, and Yanan Li prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.
Additional information
Communicated by Sanjeev Galande.
Corresponding editor: Sanjeev Galande
Rights and permissions
About this article
Cite this article
Wu, Q., Liu, L., Feng, Y. et al. UBR5 promotes migration and invasion of glioma cells by regulating the ECRG4/NF-κB pathway. J Biosci 47, 45 (2022). https://doi.org/10.1007/s12038-022-00280-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12038-022-00280-9