RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma.
NSUN5
RNA cytosine methylation
glioblastoma
protein synthesis
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
28
02
2023
received:
15
07
2022
accepted:
13
04
2023
medline:
8
9
2023
pubmed:
15
4
2023
entrez:
14
4
2023
Statut:
ppublish
Résumé
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed. In this study, we show that elevated expression of 28S rRNA (cytosine-C(5))-methyltransferase NSUN5, which methylates cytosine 3782 of 28S rRNA in GBM cells, is strongly associated with the poor survival of GBM patients. Moreover, we demonstrate that overexpression of NSUN5 increases protein synthesis in GBM cells. NSUN5 knockdown decreased protein synthesis, cell proliferation, sphere formation, migration, and resistance to temozolomide in GBM cell lines. NSUN5 knockdown also decreased the number and size of GBM neurospheres in vitro. As a corollary, mice harboring U251 tumors wherein NSUN5 was knocked down survived longer than mice harboring control tumors. Taken together, our results suggest that NSUN5 plays a protumorigenic role in GBM by enabling the enhanced protein synthesis requisite for tumor progression. Accordingly, NSUN5 may be a hitherto unappreciated target for the treatment of GBM.
Identifiants
pubmed: 37057706
doi: 10.1002/1878-0261.13434
pmc: PMC10483612
doi:
Substances chimiques
Methyltransferases
EC 2.1.1.-
RNA
63231-63-0
RNA, Ribosomal, 28S
0
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1763-1783Informations de copyright
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Int J Mol Sci. 2020 Apr 17;21(8):
pubmed: 32316617
J Clin Neurosci. 2013 Jul;20(7):907-11
pubmed: 23688441
Nat Commun. 2020 Oct 5;11(1):4997
pubmed: 33020472
Nat Cell Biol. 2019 May;21(5):552-559
pubmed: 31048770
Am J Transl Res. 2020 Jul 15;12(7):3858-3870
pubmed: 32774740
Nat Rev Cancer. 2010 Apr;10(4):254-66
pubmed: 20332778
Neurol Res Int. 2012;2012:878425
pubmed: 22530127
Nat Rev Neurol. 2010 Jan;6(1):39-51
pubmed: 19997073
Glia. 2019 Apr;67(4):688-702
pubmed: 30485550
Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):1985-96
pubmed: 25053711
Front Oncol. 2015 Nov 16;5:251
pubmed: 26636033
J Clin Invest. 2019 Mar 1;129(3):1329-1344
pubmed: 30645202
Proteomics. 2016 Sep;16(18):2448-53
pubmed: 27461997
Cancer Cell. 2006 May;9(5):391-403
pubmed: 16697959
Nucleic Acids Res. 2019 Dec 16;47(22):11807-11825
pubmed: 31722427
Cancer Drug Resist. 2021;4:17-43
pubmed: 34337348
Neurology. 2019 May 21;92(21):e2483-e2491
pubmed: 31019097
Nucleic Acids Res. 2013 Oct;41(19):9062-76
pubmed: 23913415
Sci Transl Med. 2016 Aug 31;8(354):354re3
pubmed: 27582061
Cancer Biol Ther. 2021 Dec 2;22(10-12):587-597
pubmed: 34705606
Int J Mol Sci. 2018 Jul 26;19(8):
pubmed: 30049957
Cancer Cell. 2021 Apr 12;39(4):509-528.e20
pubmed: 33577785
Trends Cancer. 2020 Mar;6(3):223-235
pubmed: 32101725
Cancers (Basel). 2022 Jan 17;14(2):
pubmed: 35053605
Cancers (Basel). 2020 Mar 20;12(3):
pubmed: 32244981
Oncologist. 2020 Nov;25(11):e1763-e1776
pubmed: 33394574
Front Neurol. 2014 Nov 03;5:220
pubmed: 25404928
Nat Rev Cancer. 2015 Oct;15(10):593-607
pubmed: 26383138
Aging (Albany NY). 2021 Jun 17;13(12):15833-15874
pubmed: 34139673
Nat Rev Mol Cell Biol. 2019 Oct;20(10):608-624
pubmed: 31520073
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Cancer Res. 2009 Dec 1;69(23):9065-72
pubmed: 19920198
J Biol Chem. 2020 Dec 25;295(52):18134-18147
pubmed: 33093178
Nutrients. 2021 Jul 30;13(8):
pubmed: 34444824
Stem Cell Reports. 2015 Jul 14;5(1):1-9
pubmed: 26095605
Nucleic Acids Res. 2010 Mar;38(5):1415-30
pubmed: 20007150
Cells. 2019 Jun 06;8(6):
pubmed: 31174389
Nucleic Acids Res. 2013 Jan;41(Database issue):D262-7
pubmed: 23118484
Gynecol Oncol. 2015 Sep;138(3):647-55
pubmed: 26186909
Cytogenet Cell Genet. 2001;95(1-2):20-7
pubmed: 11978965
Neuro Oncol. 2013 Jul;15(7):829-39
pubmed: 23502430
PLoS One. 2016 Apr 18;11(4):e0153901
pubmed: 27089539
Nucleic Acids Res. 2021 Jan 8;49(D1):D605-D612
pubmed: 33237311
Acta Neuropathol. 2019 Dec;138(6):1053-1074
pubmed: 31428936
Clin Cancer Res. 2019 Jul 15;25(14):4309-4319
pubmed: 30979743
Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12
pubmed: 25348405
Nat Commun. 2015 Jan 30;6:6158
pubmed: 25635753
Cell Signal. 2016 Aug;28(8):838-49
pubmed: 27075926
Nat Commun. 2018 Mar 21;9(1):1163
pubmed: 29563491
Mol Brain. 2019 Aug 28;12(1):74
pubmed: 31462248
EBioMedicine. 2021 Jan;63:103195
pubmed: 33418496
Sci Data. 2017 Oct 10;4:170151
pubmed: 28994825
J Biol Chem. 2019 Aug 23;294(34):12638-12654
pubmed: 31262726
Nat Protoc. 2014 Apr;9(4):751-60
pubmed: 24603934
Br J Cancer. 2010 Jun 29;103(1):29-35
pubmed: 20517307
J Neurooncol. 2016 May;127(3):427-34
pubmed: 26900075
Genes Dev. 2015 Jun 15;29(12):1203-17
pubmed: 26109046
Front Oncol. 2021 Jul 08;11:701291
pubmed: 34307170