{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:02:32Z","timestamp":1781762552820,"version":"3.54.5"},"reference-count":36,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203637"],"award-info":[{"award-number":["82203637"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Technology Development Foundation of Nanjing Medical University","award":["NMUB20210220"],"award-info":[{"award-number":["NMUB20210220"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Technol Cancer Res Treat"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Objectives: This study aimed to investigate the effect of specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1)-mediated deSUMOylation on the malignant behavior of glioma stem cells (GSCs) under hypoxia conditions and evaluate the clinical value of prevention in glioma patients. Introductions: Under hypoxic conditions, upregulated hypoxia-inducible factor 1\u03b1 (HIF1\u03b1) expression in GSCs activates Wnt\/\u03b2-catenin signaling pathways, which provide rich nutritional support for glioblastoma (GBM). SENP1-mediated deSUMOylation stabilizes the expression of HIF1\u03b1 and \u03b2-catenin, leading to the occurrence of GSCs-initiated tumorigenesis. Targeting SENP1-mediated deSUMOylation may suppress the malignancy of GSCs and disrupt GBM progression. Methods: The expression of SENP1 in different World Health Organization grades was observed by immunohistochemistry and western blot. Lentivirus-packaged SENP1shRNA downregulated the expression of SENP1 in GSCs, and the downregulated results were verified by western blotting and polymerase chain reaction. The effects of LV-SENP1shRNA on the migration and proliferation of GSCs were detected by scratch and cloning experiments. The effect of LV- SENP1shRNA on the tumor formation ability of GSCs was observed in nude mice. Immunoprecipitation clarified the mechanism of SENP1 regulating the malignant behavior of GSCs under hypoxia. The correlation between the expression level of SENP1 and the survival of glioma patients was determined by statistical analysis. Results: SENP1 expression in GSCs derived from clinical samples was upregulated in GBM. SUMOylation was observed in GSCs in vitro, and deSUMOylation, accompanied by an increase in SENP1 expression, was induced by hypoxia. SENP1 expression was downregulated in GSCs with lentivirus-mediated stable transfection, which attenuated the proliferation and differentiation of GSCs, thus diminishing tumorigenesis. Mechanistically, HIF1\u03b1 induced activation of Wnt\/\u03b2-catenin, which depended on SENP1-mediated deSUMOylation, promoting GSC-driven GBM growth under the hypoxia microenvironment. Conclusion: Our findings indicate that SENP1-mediated deSUMOylation as a feature of GSCs is essential for GBM maintenance, suggesting that targeting SENP1 against GSCs may effectively improve GBM therapeutic efficacy.<\/jats:p>","DOI":"10.1177\/15330338241257490","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:05:01Z","timestamp":1716854701000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["SENP1-Mediated deSUMOylation Regulates the Tumor Remodeling of Glioma Stem Cells Under Hypoxic Stress"],"prefix":"10.1177","volume":"23","author":[{"given":"Ping","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, 2nd Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China"},{"name":"Department of Neurosurgery, The First Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 2nd Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 2nd Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 2nd Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4565-321X","authenticated-orcid":false,"given":"Jun","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 2nd Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"bibr1-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.603911"},{"issue":"9","key":"bibr2-15330338241257490","first-page":"2613","volume":"19","author":"Witthayanuwat S","year":"2018","journal-title":"Asian Pac J Cancer Prev: APJCP"},{"key":"bibr3-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030621"},{"key":"bibr4-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110493"},{"key":"bibr5-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214224"},{"key":"bibr6-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-2270"},{"key":"bibr7-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84431"},{"key":"bibr8-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092371"},{"key":"bibr9-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-022-00433-3"},{"key":"bibr10-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05389-1"},{"key":"bibr11-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2022.113281"},{"key":"bibr12-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2023.13976"},{"key":"bibr13-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3390\/cells11050814"},{"key":"bibr14-15330338241257490","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203084"},{"key":"bibr15-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"bibr16-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.3032"},{"key":"bibr17-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1432-1"},{"key":"bibr18-15330338241257490","doi-asserted-by":"publisher","DOI":"10.7150\/thno.41692"},{"key":"bibr19-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.03.023"},{"key":"bibr20-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104872"},{"key":"bibr21-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2022.103056"},{"key":"bibr22-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-017-0045-7"},{"key":"bibr23-15330338241257490","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.65653"},{"key":"bibr24-15330338241257490","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.58035"},{"key":"bibr25-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117859"},{"key":"bibr26-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24619-2"},{"key":"bibr27-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34993-0"},{"key":"bibr28-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121821"},{"key":"bibr29-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-1456"},{"key":"bibr30-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100227"},{"key":"bibr31-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01638-1"},{"key":"bibr32-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14133165"},{"key":"bibr33-15330338241257490","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102700"},{"key":"bibr34-15330338241257490","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030473"},{"key":"bibr35-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02689-4"},{"key":"bibr36-15330338241257490","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2021.07.007"}],"container-title":["Technology in Cancer Research &amp; Treatment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15330338241257490","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15330338241257490","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15330338241257490","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:14:53Z","timestamp":1777702493000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15330338241257490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":36,"alternative-id":["10.1177\/15330338241257490"],"URL":"https:\/\/doi.org\/10.1177\/15330338241257490","relation":{},"ISSN":["1533-0346","1533-0338"],"issn-type":[{"value":"1533-0346","type":"print"},{"value":"1533-0338","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"article-number":"15330338241257490"}}