Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/33984142http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33984142http://www.w3.org/2000/01/rdf-schema#comment"

Background

Ferroptosis, a programmed cell death characterized by lipid peroxidation, is implicated in various diseases including cancer. Although cell density-dependent E-cadherin and Merlin/Neurofibromin (NF2) loss can modulate ferroptosis, the role of ferroptosis and its potential link to NF2 status and E-cadherin expression in meningioma remain unknown.

Methods

Relationship between ferroptosis modulators expression and NF2 mutational status was examined in 35 meningiomas (10 NF2 loss and 25 NF2 wild type). The impact of NF2 and E-cadherin on ferroptosis were examined by lactate dehydrogenase (LDH) release, lipid peroxidation, and western blot assays in IOMM-Lee, CH157, and patient-derived meningioma cell models. Luciferase reporter and chromatin immunoprecipitation assays were used to assess the ability of MEF2C (myocyte enhancer factor 2C) to drive expression of NF2 and CDH1 (E-cadherin). Therapeutic efficacy of Erastin-induced ferroptosis was tested in xenograft mouse models.

Results

Meningioma cells with NF2 inactivation were susceptible to Erastin-induced ferroptosis. Meningioma cells grown at higher density increased expression of E-cadherin, which suppressed Erastin-induced ferroptosis. Maintaining NF2 and E-cadherin inhibited ferroptosis-related lipid peroxidation and meningioma cell death. MEF2C was found to drive the expression of both NF2 and E-cadherin. MEF2C silencing enhanced Erastin-induced ferroptotic meningioma cell death and lipid peroxidation levels in vitro, which was limited by forced expression of MEF2C targets, NF2 and E-cadherin. In vivo, anti-meningioma effect of Erastin was augmented by MEF2C knockdown and was counteracted by NF2 or E-cadherin.

Conclusions

NF2 loss and low E-cadherin create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.org/dc/terms/identifier"doi:10.1093/neuonc/noab114"xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Bao Z."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Gong Y."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Ji J."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Li C."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Wang D."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Xie Q."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Ye Y."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Wakimoto H."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/author"Hua L."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/name"Neuro Oncol"xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/pages"2014-2027"xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/title"MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma."xsd:string
http://purl.uniprot.org/citations/33984142http://purl.uniprot.org/core/volume"23"xsd:string
http://purl.uniprot.org/citations/33984142http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33984142
http://purl.uniprot.org/citations/33984142http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33984142
http://purl.uniprot.org/uniprot/#_A0A0D9SFD0-mappedCitation-33984142http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33984142
http://purl.uniprot.org/uniprot/#_B2R681-mappedCitation-33984142http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33984142
http://purl.uniprot.org/uniprot/#_D8L7E9-mappedCitation-33984142http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33984142
http://purl.uniprot.org/uniprot/#_Q06413-mappedCitation-33984142http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33984142
http://purl.uniprot.org/uniprot/Q06413http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33984142
http://purl.uniprot.org/uniprot/A0A0D9SFD0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33984142
▶