{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:48:55Z","timestamp":1785905335369,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004763","name":"Natural Science Foundation of Inner Mongolia","doi-asserted-by":"publisher","award":["2024LHMS08022"],"award-info":[{"award-number":["2024LHMS08022"]}],"id":[{"id":"10.13039\/501100004763","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Inner Mongolia Key Research and Development Program","award":["YF20240065"],"award-info":[{"award-number":["YF20240065"]}]},{"DOI":"10.13039\/501100005046","name":"Heilongjiang Provincial Natural Science Foundation of China","doi-asserted-by":"crossref","award":["LH2023H011"],"award-info":[{"award-number":["LH2023H011"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Glioblastoma (GBM) is a highly aggressive primary malignant brain tumor, featuring diffuse infiltrative growth and poor clinical outcomes, which underscores the need to delineate the molecular mechanisms driving its malignant progression. COP9 signalosome subunit 7B (COPS7B), a core component of the conserved COP9 signalosome complex, is significantly upregulated in GBM tissues; however, its biological function and regulatory mechanism in GBM remain largely elusive. Here, we found that elevated COPS7B expression was positively correlated with glioma pathological grade and adverse prognosis in histologically and molecularly confirmed GBM patients. Functional assays demonstrated that COPS7B markedly promoted the proliferation, migration, and invasion of GBM cells in vitro, while COPS7B knockdown exerted the opposite suppressive effects. Mechanistically, we identified clusterin (CLU) as a key downstream functional effector of COPS7B in GBM. COPS7B upregulated CLU protein abundance by enhancing the translation efficiency of CLU mRNA, without altering its transcriptional level or protein stability. Functional rescue experiments further confirmed that CLU is indispensable for COPS7B-mediated malignancy-driving phenotypes in GBM, and transcriptomic analysis revealed that the progression-promoting effect of CLU was tightly associated with the activation of tumor-related signaling cascades, including the ERK and MAPK pathways, as well as the regulation of cell growth, invasion, and migration. Collectively, this study not only reveals a critical role of COPS7B in driving GBM malignant progression but also delineates a novel COPS7B-CLU regulatory axis that drives GBM aggressive phenotypes via activation of mitogenic signaling, suggesting candidate targets for further translational investigation.<\/jats:p>","DOI":"10.3390\/ijms27156976","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:16:27Z","timestamp":1785766587000},"page":"6976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["COPS7B Drives Malignant Progression of Glioblastoma Through Translational Upregulation of the Downstream Functional Effector CLU"],"prefix":"10.3390","volume":"27","author":[{"given":"Jiarui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Liu","sequence":"additional","affiliation":[{"name":"Ordos Clinical Medical College, Inner Mongolia Medical University, Ordos 017000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunting","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozhan","family":"Fan","sequence":"additional","affiliation":[{"name":"Ordos Clinical Medical College, Inner Mongolia Medical University, Ordos 017000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoshuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105780","DOI":"10.1016\/j.phrs.2021.105780","article-title":"Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance","volume":"171","author":"Wu","year":"2021","journal-title":"Pharmacol. 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