Yin Yang 1-Induced Long Noncoding RNA DUXAP9 Drives the Progression of Oral Squamous Cell Carcinoma by Blocking CDK1-Mediated EZH2 Degradation.
Humans
Carcinoma, Squamous Cell
/ metabolism
Squamous Cell Carcinoma of Head and Neck
/ genetics
RNA, Long Noncoding
/ genetics
Yin-Yang
Cell Line, Tumor
Cell Proliferation
/ genetics
Mouth Neoplasms
/ genetics
Head and Neck Neoplasms
Enhancer of Zeste Homolog 2 Protein
/ genetics
CDC2 Protein Kinase
EZH2
LncRNA DUXAP9
Yin Yang 1 (YY1)
oral squamous cell carcinoma
ubiquitination
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
04
04
2023
received:
20
12
2022
medline:
6
9
2023
pubmed:
4
7
2023
entrez:
4
7
2023
Statut:
ppublish
Résumé
LncRNAs play a critical role in oral squamous cell carcinoma (OSCC) progression. However, the function and detailed molecular mechanism of most lncRNAs in OSCC are not fully understood. Here, a novel nuclear-localized lncRNA, DUXAP9 (DUXAP9), that is highly expressed in OSCC is identified. A high level of DUXAP9 is positively associated with lymph node metastasis, poor pathological differentiation, advanced clinical stage, worse overall survival, and worse disease-specific survival in OSCC patients. Overexpression of DUXAP9 significantly promotes OSCC cell proliferation, migration, invasion, and xenograft tumor growth and metastasis, and upregulates N-cadherin, Vimentin, Ki67, PCNA, and EZH2 expression and downregulates E-cadherin in vitro and in vivo, whereas knockdown of DUXAP9 remarkably suppresses OSCC cell proliferation, migration, invasion, and xenograft tumor growth in vitro and in vivo in an EZH2-dependent manner. Yin Yang 1 (YY1) is found to activate the transcriptional expression of DUXAP9 in OSCC. Furthermore, DUXAP9 physically interacts with EZH2 and inhibits EZH2 degradation via the suppression of EZH2 phosphorylation, thereby blocking EZH2 translocation from the nucleus to the cytoplasm. Thus, DUXAP9 can serve as a promising target for OSCC therapy.
Identifiants
pubmed: 37401236
doi: 10.1002/advs.202207549
pmc: PMC10477890
doi:
Substances chimiques
RNA, Long Noncoding
0
EZH2 protein, human
EC 2.1.1.43
Enhancer of Zeste Homolog 2 Protein
EC 2.1.1.43
CDK1 protein, human
EC 2.7.11.22
CDC2 Protein Kinase
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2207549Subventions
Organisme : National Natural Science Foundation of China
ID : 82272816
Organisme : National Natural Science Foundation of China
ID : 81972589
Organisme : National Natural Science Foundation of China
ID : 82070894
Organisme : Innovation research team of high-level local universities in Shanghai
ID : SHSMU-ZDCX20212802
Organisme : Innovation research team of high-level local universities in Shanghai
ID : SHSMU-ZDCX20212501
Organisme : Science and Technology Commission of Shanghai Municipality
ID : 21ZR1436500
Organisme : Science and Technology Commission of Shanghai Municipality
ID : 22ZR1479800
Organisme : Science and Technology Innovation Plan Of Shanghai Science and Technology Commission
ID : 22ZR1479800
Informations de copyright
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
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