GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma

BackgroundGlioma is a lethal primary tumor of central nervous system. Ferroptosis is a newly identified form of necrotic cell death. Triggering ferroptosis has shown potential to eliminate aggressive tumors. GPX7, a member of glutathione peroxidase family (GPXs), has been described to participate in...

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Main Authors: Yan Zhou, Haiyang Wu, Fanchen Wang, Lixia Xu, Yan Yan, Xiaoguang Tong, Hua Yan
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.802124/full
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author Yan Zhou
Haiyang Wu
Fanchen Wang
Lixia Xu
Yan Yan
Xiaoguang Tong
Xiaoguang Tong
Hua Yan
Hua Yan
author_facet Yan Zhou
Haiyang Wu
Fanchen Wang
Lixia Xu
Yan Yan
Xiaoguang Tong
Xiaoguang Tong
Hua Yan
Hua Yan
author_sort Yan Zhou
collection DOAJ
description BackgroundGlioma is a lethal primary tumor of central nervous system. Ferroptosis is a newly identified form of necrotic cell death. Triggering ferroptosis has shown potential to eliminate aggressive tumors. GPX7, a member of glutathione peroxidase family (GPXs), has been described to participate in oxidative stress and tumorigenesis. However, the biological functions of GPX7 in glioma are still unknown.MethodsBioinformatics method was used to assess the prognostic role of GPX7 in glioma. CCK8, wound healing, transwell and cell apoptosis assays were performed to explore the functions of GPX7 in glioma cells. In vivo experiment was also conducted to confirm in vitro findings. Ferroptosis-related assays were carried out to investigate the association between GPX7 and ferroptosis in glioma.ResultsGPX7 was aberrantly expressed in glioma and higher expression of GPX7 was correlated with adverse outcomes. GPX7 silencing enhanced ferroptosis-related oxidative stress in glioma cells and the loss of GXP7 sensitized glioma to ferroptosis induced by erastin. Furthermore, we found that miR-29b directly suppressed GPX7 expression post-transcriptionally. Reconstitution of miR-29b enhanced erastin sensitivity, partly via GPX7 suppression.ConclusionsOur study clarified the prognostic role of GPX7 in glioma and preliminarily revealed the role of GPX7 in ferroptosis, which may be conducive to the exploration of therapeutic targets of glioma.
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spelling doaj.art-7c03fed749274533b870868a30194ba12022-12-21T21:23:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.802124802124GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in GliomaYan Zhou0Haiyang Wu1Fanchen Wang2Lixia Xu3Yan Yan4Xiaoguang Tong5Xiaoguang Tong6Hua Yan7Hua Yan8Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, ChinaClinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, ChinaClinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, ChinaClinical Laboratory, Tianjin Huanhu Hospital, Tianjin, ChinaClinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, ChinaClinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, ChinaBackgroundGlioma is a lethal primary tumor of central nervous system. Ferroptosis is a newly identified form of necrotic cell death. Triggering ferroptosis has shown potential to eliminate aggressive tumors. GPX7, a member of glutathione peroxidase family (GPXs), has been described to participate in oxidative stress and tumorigenesis. However, the biological functions of GPX7 in glioma are still unknown.MethodsBioinformatics method was used to assess the prognostic role of GPX7 in glioma. CCK8, wound healing, transwell and cell apoptosis assays were performed to explore the functions of GPX7 in glioma cells. In vivo experiment was also conducted to confirm in vitro findings. Ferroptosis-related assays were carried out to investigate the association between GPX7 and ferroptosis in glioma.ResultsGPX7 was aberrantly expressed in glioma and higher expression of GPX7 was correlated with adverse outcomes. GPX7 silencing enhanced ferroptosis-related oxidative stress in glioma cells and the loss of GXP7 sensitized glioma to ferroptosis induced by erastin. Furthermore, we found that miR-29b directly suppressed GPX7 expression post-transcriptionally. Reconstitution of miR-29b enhanced erastin sensitivity, partly via GPX7 suppression.ConclusionsOur study clarified the prognostic role of GPX7 in glioma and preliminarily revealed the role of GPX7 in ferroptosis, which may be conducive to the exploration of therapeutic targets of glioma.https://www.frontiersin.org/articles/10.3389/fonc.2021.802124/fullbioinformaticsferroptosisgliomaGPX7miR-29b
spellingShingle Yan Zhou
Haiyang Wu
Fanchen Wang
Lixia Xu
Yan Yan
Xiaoguang Tong
Xiaoguang Tong
Hua Yan
Hua Yan
GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma
Frontiers in Oncology
bioinformatics
ferroptosis
glioma
GPX7
miR-29b
title GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma
title_full GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma
title_fullStr GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma
title_full_unstemmed GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma
title_short GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma
title_sort gpx7 is targeted by mir 29b and gpx7 knockdown enhances ferroptosis induced by erastin in glioma
topic bioinformatics
ferroptosis
glioma
GPX7
miR-29b
url https://www.frontiersin.org/articles/10.3389/fonc.2021.802124/full
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