FHOD1 is upregulated in glioma cells and attenuates ferroptosis of glioma cells by targeting HSPB1 signaling.
FHOD1
HSPB1
ferroptosis
glioma
prognosis
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
09
04
2023
received:
18
02
2023
accepted:
11
04
2023
medline:
23
10
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
ppublish
Résumé
As a new type of regulatory cell death, ferroptosis has been proven to be involved in cancer pathogenesis and therapeutic response. However, the detailed roles of ferroptosis or ferroptosis-associated genes in glioma remain to be clarified. Here, we performed the TMT/iTRAQ-Based Quantitative Proteomic Approach to identify the differentially expressed proteins between glioma specimens and adjacent tissues. Kaplan-Meier survival was used to estimate the survival values. We also explored the regulatory roles of abnormally expressed formin homology 2 domain-containing protein 1 (FHOD1) in glioma ferroptosis sensitivity. In our study, FHOD1 was identified to be the most significantly upregulated protein in glioma tissues. Multiple glioma datasets revealed that the glioma patients with low FHOD1 expression displayed favorable survival time. Functional analysis proved that the knockdown of FHOD1 inhibited cell growth and improved the cellular sensitivity to ferroptosis in glioma cells T98G and U251. Mechanically, we found the up-regulation and hypomethylation of HSPB1, a negative regulator of ferroptosis, in glioma tissues. FHOD1 knockdown could enhance the ferroptosis sensitivity of glioma cells via up-regulating the methylated heat-shock protein B (HSPB1). Overexpression of HSPB1 significantly reversed FHOD1 knockdown-mediated ferroptosis. In summary, this study demonstrated that the FHOD1-HSPB1 axis exerts marked regulatory effects on ferroptosis, and might affect the prognosis and therapeutic response in glioma.
Sections du résumé
BACKGROUND
As a new type of regulatory cell death, ferroptosis has been proven to be involved in cancer pathogenesis and therapeutic response. However, the detailed roles of ferroptosis or ferroptosis-associated genes in glioma remain to be clarified.
METHODS
Here, we performed the TMT/iTRAQ-Based Quantitative Proteomic Approach to identify the differentially expressed proteins between glioma specimens and adjacent tissues. Kaplan-Meier survival was used to estimate the survival values. We also explored the regulatory roles of abnormally expressed formin homology 2 domain-containing protein 1 (FHOD1) in glioma ferroptosis sensitivity.
RESULTS
In our study, FHOD1 was identified to be the most significantly upregulated protein in glioma tissues. Multiple glioma datasets revealed that the glioma patients with low FHOD1 expression displayed favorable survival time. Functional analysis proved that the knockdown of FHOD1 inhibited cell growth and improved the cellular sensitivity to ferroptosis in glioma cells T98G and U251. Mechanically, we found the up-regulation and hypomethylation of HSPB1, a negative regulator of ferroptosis, in glioma tissues. FHOD1 knockdown could enhance the ferroptosis sensitivity of glioma cells via up-regulating the methylated heat-shock protein B (HSPB1). Overexpression of HSPB1 significantly reversed FHOD1 knockdown-mediated ferroptosis.
CONCLUSIONS
In summary, this study demonstrated that the FHOD1-HSPB1 axis exerts marked regulatory effects on ferroptosis, and might affect the prognosis and therapeutic response in glioma.
Identifiants
pubmed: 37211949
doi: 10.1111/cns.14264
pmc: PMC10580363
doi:
Substances chimiques
Heat-Shock Proteins
0
FHOD1 protein, human
0
Formins
0
Fetal Proteins
0
HSPB1 protein, human
0
Molecular Chaperones
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3351-3363Informations de copyright
© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
Références
Cancers (Basel). 2021 Dec 28;14(1):
pubmed: 35008294
J Nanobiotechnology. 2022 Mar 27;20(1):161
pubmed: 35351131
Pharmacol Res. 2021 Sep;171:105780
pubmed: 34302977
Cancers (Basel). 2022 Sep 24;14(19):
pubmed: 36230565
Oxid Med Cell Longev. 2022 Nov 18;2022:7862430
pubmed: 36439690
Sci Data. 2018 Aug 14;5:180158
pubmed: 30106394
CNS Neurosci Ther. 2023 Nov;29(11):3351-3363
pubmed: 37211949
Clin Transl Med. 2021 Apr;11(4):e390
pubmed: 33931967
Neoplasia. 2022 Mar;25:18-27
pubmed: 35078134
Breast Cancer (Auckl). 2018 Aug 24;12:1178223418792247
pubmed: 30158824
Front Genet. 2021 Nov 08;12:753680
pubmed: 34819946
Aging Dis. 2022 Oct 1;13(5):1348-1364
pubmed: 36186133
Endocr Relat Cancer. 2022 Sep 30;29(11):615-624
pubmed: 36040830
Front Genet. 2022 Nov 11;13:948290
pubmed: 36437923
Cancers (Basel). 2020 Nov 05;12(11):
pubmed: 33167414
Lab Invest. 2022 Dec;102(12):1323-1334
pubmed: 35945269
CNS Neurosci Ther. 2022 Dec;28(12):2104-2115
pubmed: 35962621
Front Genet. 2021 Mar 30;12:649270
pubmed: 33859674
Cancer Metab. 2015 Jan 25;3(1):1
pubmed: 25621173
J Biomed Sci. 2023 Jan 10;30(1):3
pubmed: 36627707
Apoptosis. 2006 Nov;11(11):1863-76
pubmed: 17013756
Genes Dis. 2020 Sep 29;9(2):334-346
pubmed: 35224150
Front Immunol. 2021 Sep 17;12:719175
pubmed: 34603293
J Nanobiotechnology. 2022 Nov 3;20(1):467
pubmed: 36329436
J Oncol. 2022 Dec 28;2022:6093216
pubmed: 36618071
Pharmacol Res. 2022 May;179:106218
pubmed: 35413423
Cancer Res. 2009 Dec 1;69(23):9065-72
pubmed: 19920198
Genomics Proteomics Bioinformatics. 2021 Feb;19(1):1-12
pubmed: 33662628
J Cancer. 2022 May 20;13(8):2683-2693
pubmed: 35711838
Cell Death Dis. 2022 Dec 24;13(12):1071
pubmed: 36566214
Clin Transl Med. 2022 Sep;12(9):e1013
pubmed: 36149747
J Neurophysiol. 2022 Dec 1;128(6):1507-1517
pubmed: 36321738
Front Immunol. 2022 Feb 24;13:834595
pubmed: 35281049
Genes Dis. 2020 May 18;8(3):241-249
pubmed: 33997171
Genes Dis. 2020 Dec 04;9(2):347-357
pubmed: 35224151
Sci Rep. 2021 Dec 8;11(1):23694
pubmed: 34880375
J Exp Clin Cancer Res. 2022 Oct 20;41(1):307
pubmed: 36266731
Clin Transl Oncol. 2023 May;25(5):1378-1388
pubmed: 36484954
Sci Rep. 2021 Apr 6;11(1):7548
pubmed: 33824419
J Inflamm Res. 2021 Oct 18;14:5393-5401
pubmed: 34703276
J Clin Invest. 2023 Jan 3;133(1):
pubmed: 36594473
PLoS One. 2013 Sep 26;8(9):e74923
pubmed: 24086398
Cell Rep. 2020 May 26;31(8):107681
pubmed: 32460023
J Cell Sci. 2014 Apr 1;127(Pt 7):1379-93
pubmed: 24481812