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Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma

Chemoresistance in patients with glioblastoma multiforme (GBM) is a common reason hindering the success of treatment. Recently, ferroptosis has been reported to be associated with chemoresistance in different types of cancer, while the role of ferroptosis‐related genes in GBM have not been fully elu...

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Autores principales: Yao, Lei, Li, Juanni, Zhang, Xiaofang, Zhou, Lei, Hu, Kuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627366/
https://www.ncbi.nlm.nih.gov/pubmed/35962621
http://dx.doi.org/10.1111/cns.13945
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author Yao, Lei
Li, Juanni
Zhang, Xiaofang
Zhou, Lei
Hu, Kuan
author_facet Yao, Lei
Li, Juanni
Zhang, Xiaofang
Zhou, Lei
Hu, Kuan
author_sort Yao, Lei
collection PubMed
description Chemoresistance in patients with glioblastoma multiforme (GBM) is a common reason hindering the success of treatment. Recently, ferroptosis has been reported to be associated with chemoresistance in different types of cancer, while the role of ferroptosis‐related genes in GBM have not been fully elucidated. This study aimed to demonstrate the roles and mechanism of ferroptosis‐related genes in chemoresistance and metastasis of GBM. First, two candidate genes, squalene epoxidase (SQLE) and FANCD2, were identified to be associated with ferroptosis‐related chemoresistance in GBM from three temozolomide (TMZ) therapeutic datasets and one ferroptosis‐related gene dataset. Then, comprehensive bio‐informatics data from different databases testified that SQLE was significantly downregulated both in GBM tissue and cells and displayed a better prognosis in GBM. Clinical data identified lower expression of SQLE was significantly associated with WHO grade and 1p/19q codeletion. Moreover, through in vitro experiments, SQLE was confirmed to suppress ERK‐mediated TMZ chemoresistance and metastasis of GBM cells. The KEGG analysis of SQLE‐associated co‐expressed genes indicated SQLE was potentially involved in the cell cycle. Furthermore, SQLE was found to have the most significant correlations with tumor‐infiltrating lymphocytes and immunomodulators. These findings highlighted that SQLE could be a potential target and a biomarker for therapy and prognosis of patients with GBM.
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spelling pubmed-96273662022-11-03 Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma Yao, Lei Li, Juanni Zhang, Xiaofang Zhou, Lei Hu, Kuan CNS Neurosci Ther Original Articles Chemoresistance in patients with glioblastoma multiforme (GBM) is a common reason hindering the success of treatment. Recently, ferroptosis has been reported to be associated with chemoresistance in different types of cancer, while the role of ferroptosis‐related genes in GBM have not been fully elucidated. This study aimed to demonstrate the roles and mechanism of ferroptosis‐related genes in chemoresistance and metastasis of GBM. First, two candidate genes, squalene epoxidase (SQLE) and FANCD2, were identified to be associated with ferroptosis‐related chemoresistance in GBM from three temozolomide (TMZ) therapeutic datasets and one ferroptosis‐related gene dataset. Then, comprehensive bio‐informatics data from different databases testified that SQLE was significantly downregulated both in GBM tissue and cells and displayed a better prognosis in GBM. Clinical data identified lower expression of SQLE was significantly associated with WHO grade and 1p/19q codeletion. Moreover, through in vitro experiments, SQLE was confirmed to suppress ERK‐mediated TMZ chemoresistance and metastasis of GBM cells. The KEGG analysis of SQLE‐associated co‐expressed genes indicated SQLE was potentially involved in the cell cycle. Furthermore, SQLE was found to have the most significant correlations with tumor‐infiltrating lymphocytes and immunomodulators. These findings highlighted that SQLE could be a potential target and a biomarker for therapy and prognosis of patients with GBM. John Wiley and Sons Inc. 2022-08-13 /pmc/articles/PMC9627366/ /pubmed/35962621 http://dx.doi.org/10.1111/cns.13945 Text en © 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Yao, Lei
Li, Juanni
Zhang, Xiaofang
Zhou, Lei
Hu, Kuan
Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma
title Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma
title_full Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma
title_fullStr Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma
title_full_unstemmed Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma
title_short Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma
title_sort downregulated ferroptosis‐related gene sqle facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627366/
https://www.ncbi.nlm.nih.gov/pubmed/35962621
http://dx.doi.org/10.1111/cns.13945
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