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Yin Yang 1-Induced Long Noncoding RNA DUXAP9 Drives the Progression of Oral Squamous Cell Carcinoma by Blocking
Wenkai Zhou1,2, Yisheng Feng2, Chengzhong Lin2,3
1Department of Oral and Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Abstract:
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.
Insights
A novel long non-coding RNA, DUXAP9, promotes oral squamous cell carcinoma (OSCC) progression by stabilizing EZH2. Targeting DUXAP9 may offer a new therapeutic strategy for OSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are crucial in cancer, but their roles in oral squamous cell carcinoma (OSCC) are not fully elucidated.
- Understanding lncRNA functions is vital for developing novel OSCC therapies.
Purpose of the Study:
- To identify and characterize a novel lncRNA, DUXAP9, in OSCC.
- To investigate the molecular mechanisms underlying DUXAP9's role in OSCC progression.
- To evaluate DUXAP9 as a potential therapeutic target for OSCC.
Main Methods:
- Identification and expression analysis of DUXAP9 in OSCC tissues and cell lines.
- In vitro and in vivo experiments to assess the functional role of DUXAP9 in OSCC cell proliferation, migration, and invasion.
- Investigation of DUXAP9's interaction with EZH2 and its downstream targets.
- Analysis of the correlation between DUXAP9 expression and clinical parameters in OSCC patients.
Main Results:
- DUXAP9 is highly expressed in OSCC and its high expression correlates with advanced clinical stage, lymph node metastasis, and poor patient survival.
- Overexpression of DUXAP9 promotes OSCC cell proliferation, migration, invasion, and tumor growth, while its knockdown suppresses these processes.
- DUXAP9 stabilizes EZH2 by inhibiting its phosphorylation and subsequent degradation, thereby promoting OSCC progression in an EZH2-dependent manner.
- Yin Yang 1 (YY1) was identified as a transcriptional activator of DUXAP9.
Conclusions:
- DUXAP9 is a novel oncogenic lncRNA that drives OSCC progression through the DUXAP9/EZH2 axis.
- DUXAP9 expression levels are associated with poor prognosis in OSCC patients.
- DUXAP9 represents a promising therapeutic target for oral squamous cell carcinoma.
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