Evidence map›Paper›PMID 33984142›Full record

ArticleNeuro-oncology2021

MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma.

Zhongyuan Bao, Lingyang Hua, Yangfan Ye, Daijun Wang, Chong Li, Qing Xie, Hiroaki Wakimoto, Ye Gong, Jing Ji

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Zhongyuan BaoDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Lingyang HuaDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yangfan YeDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Daijun WangDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Chong LiDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Qing XieDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Hiroaki WakimotoBrain Tumor Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ye GongDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Jing JiDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jiangsu Province Hospital · CNFudan University · CNHuashan Hospital · CNHarvard University · USNanjing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFerroptosis, 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.

methodsRelationship 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.

resultsMeningioma 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.

conclusionsNF2 loss and low E-cadherin create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.

Indexed as

FerroptosisMEF2 Transcription FactorsMeningeal NeoplasmsMeningiomaAnimalsAntigens, CDCadherinsCell Line, TumorGene SilencingHumansMiceNeurofibromin 2PiperazinesXenograft Model Antitumor AssaysAntigens, CDCadherinsCDH1 protein, humanerastinMEF2C protein, humanMEF2 Transcription FactorsNeurofibromin 2NF2 protein, humanPiperazinesE-cadherinferroptosisMEF2CmeningiomaNF2

Identifiers

PMID33984142
PMCPMC8643460
OpenAlexW3163287525

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.