Evidence map›Paper›PMID 37822160›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023

FBXO7 Confers Mesenchymal Properties and Chemoresistance in Glioblastoma by Controlling Rbfox2-Mediated Alternative Splicing.

Shangbiao Li, Yanwen Chen, Yuxin Xie, Hongchao Zhan, Yu Zeng, Kunlin Zeng, Li Wang, Ziling Zhan, Cuiying Li, Liqian Zhao and 7 more

Open access · goldAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Shangbiao LiDepartment of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Yanwen ChenDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Yuxin XieDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Hongchao ZhanDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Yu ZengDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Kunlin ZengDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Li WangDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Ziling ZhanDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Cuiying LiDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Liqian ZhaoDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Xiaoxia ChenDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Yujing TanDepartment of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Zhongyong WangDepartment of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Junguo BuDepartment of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Ye SongDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Fan DengDepartment of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Aidong ZhouDepartment of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.ORCID 0000-0001-8389-9522
Southern Medical University · CNZhujiang Hospital · CNNanfang Hospital · CNSoochow University · CN

Funding

National Natural Science Foundation of China 31871406National Natural Science Foundation of China 82003209Natural Science Foundation of Guangdong Province 2021A1515011067Natural Science Foundation of Guangdong Province 2023A1515010419Science and Technology Program of Guangzhou 202102080072
6 · The paper itself

Abstract

Mesenchymal glioblastoma (GBM) is highly resistant to radio-and chemotherapy and correlates with worse survival outcomes in GBM patients; however, the underlying mechanism determining the mesenchymal phenotype remains largely unclear. Herein, it is revealed that FBXO7, a substrate-recognition component of the SCF complex implicated in the pathogenesis of Parkinson's disease, confers mesenchymal properties and chemoresistance in GBM by controlling Rbfox2-mediated alternative splicing. Specifically, FBXO7 ubiquitinates Rbfox2 Lys249 through K63-linked ubiquitin chains upon arginine dimethylation at Arg341 and Arg441 by PRMT5, leading to Rbfox2 stabilization. FBXO7 controls Rbfox2-mediated splicing of mesenchymal genes, including FoxM1, Mta1, and Postn. FBXO7-induced exon Va inclusion of FoxM1 promotes FoxM1 phosphorylation by MEK1 and nuclear translocation, thereby upregulates CD44, CD9, and ID1 levels, resulting in GBM stem cell self-renewal and mesenchymal transformation. Moreover, FBXO7 is stabilized by temozolomide, and FBXO7 depletion sensitizes tumor xenografts in mice to chemotherapy. The findings demonstrate that the FBXO7-Rbfox2 axis-mediated splicing contributes to mesenchymal transformation and tumorigenesis, and targeting FBXO7 represents a potential strategy for GBM treatment.

Indexed as

F-Box ProteinsGlioblastomaAlternative SplicingAnimalsDrug Resistance, NeoplasmHumansMiceProtein-Arginine N-MethyltransferasesRepressor ProteinsRNA SplicingRNA Splicing FactorsTrans-ActivatorsF-Box ProteinsFBXO7 protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesRBFOX2 protein, humanRepressor ProteinsRNA Splicing FactorsTrans-Activatorsalternative splicingchemoresistanceFBXO7glioblastomamesenchymal transformation

Identifiers

PMID37822160
PMCPMC10667838
OpenAlexW4387562983

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.