THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification.
Humans
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Chaperonin Containing TCP-1
/ metabolism
Gene Expression Regulation, Neoplastic
Lung
/ metabolism
Lung Neoplasms
/ genetics
Phosphofructokinase-2
/ genetics
Phosphoric Monoester Hydrolases
/ metabolism
RNA, Messenger
/ genetics
Y-Box-Binding Protein 1
/ genetics
RNA-Binding Proteins
/ genetics
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
27 07 2023
27 07 2023
Historique:
received:
08
01
2023
accepted:
17
07
2023
revised:
13
07
2023
medline:
31
7
2023
pubmed:
28
7
2023
entrez:
27
7
2023
Statut:
epublish
Résumé
The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carcinoma (LUSC) and negatively associated with prognosis. THOC3 knockdown inhibited LUSC cell growth, migration, and glycolysis. THOC3 expression was regulated by TRiC proteins, such as CCT8 and CCT6A, which supported protein folding. Furthermore, THOC3 could form a complex with YBX1 to promote PFKFB4 transcription. THOC3 was responsible for exporting PFKFB4 mRNA to the cytoplasm, while YBX1 ensured the stability of PFKFB4 mRNA by recognizing m5C sites in its 3'UTR. Downregulation of PFKFB4 suppressed the biological activities of LUSC. Collectively, these findings suggest that THOC3, folded by CCT proteins can collaborate with YBX1 to maintain PFKFB4 expression and facilitate LUSC development. Therefore, THOC3 could be considered as a novel promising therapeutic target for LUSC.
Identifiants
pubmed: 37500615
doi: 10.1038/s41419-023-06008-3
pii: 10.1038/s41419-023-06008-3
pmc: PMC10374565
doi:
Substances chimiques
CCT6A protein, human
0
Chaperonin Containing TCP-1
EC 3.6.1.-
PFKFB4 protein, human
0
Phosphofructokinase-2
EC 2.7.1.105
Phosphoric Monoester Hydrolases
EC 3.1.3.2
RNA, Messenger
0
Y-Box-Binding Protein 1
0
YBX1 protein, human
0
Tex1 protein, human
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
475Informations de copyright
© 2023. The Author(s).
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