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dc.contributor.authorZhang, Yulin
dc.contributor.authorKong, Yang
dc.contributor.authorMa, Yuan
dc.contributor.authorNi, Shilei
dc.contributor.authorWikerholmen, Tobias Espedal
dc.contributor.authorXi, Kaiyan
dc.contributor.authorZhao, Feihu
dc.contributor.authorZhao, Zhimin
dc.contributor.authorWang, Junpeng
dc.contributor.authorHuang, Bin
dc.contributor.authorChen, Anjing
dc.contributor.authorYao, Zhong
dc.contributor.authorHan, Mingzhi
dc.contributor.authorFeng, Zichao
dc.contributor.authorHu, Yaotian
dc.contributor.authorThorsen, Frits
dc.contributor.authorWang, Jiang
dc.contributor.authorLi, Xingang
dc.description.abstractDysregulated iron metabolism is a hallmark of many cancers, including glioblastoma (GBM). However, its role in tumor progression remains unclear. Herein, we identified coatomer protein complex subunit zeta 1 (COPZ1) as a therapeutic target candidate which significantly dysregulated iron metabolism in GBM cells. Overexpression of COPZ1 was associated with increasing tumor grade and poor prognosis in glioma patients based on analysis of expression data from the publicly available database The Cancer Genome Atlas (P < 0.001). Protein levels of COPZ1 were significantly increased in GBM compared to non-neoplastic brain tissue samples in immunohistochemistry and western blot analysis. SiRNA knockdown of COPZ1 suppressed proliferation of U87MG, U251 and P3#GBM in vitro. Stable expression of a COPZ1 shRNA construct in U87MG inhibited tumor growth in vivo by ~60% relative to controls at day 21 after implantation (P < 0.001). Kaplan–Meier analysis of the survival data demonstrated that the overall survival of tumor bearing animals increased from 20.8 days (control) to 27.8 days (knockdown, P < 0.05). COPZ1 knockdown also led to the increase in nuclear receptor coactivator 4 (NCOA4), resulting in the degradation of ferritin, and a subsequent increase in the intracellular levels of ferrous iron and ultimately ferroptosis. These data demonstrate that COPZ1 is a critical mediator in iron metabolism. The COPZ1/NCOA4/FTH1 axis is therefore a novel therapeutic target for the treatment of human GBM.en_US
dc.publisherSpringer Natureen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleLoss of COPZ1 induces NCOA4 mediated autophagy and ferroptosis in glioblastoma cell linesen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2021 the authorsen_US
dc.identifier.citationOncogene. 2021, 40, 1425-1439.en_US

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