Cuproptosis-related lncRNA JPX regulates malignant cell behavior and epithelial-immune interaction in head and neck squamous cell carcinoma via miR-193b-3p/PLAU axis.
10.1038/s41368-024-00314-y
- Author:
Mouyuan SUN
1
;
Ning ZHAN
1
;
Zhan YANG
1
;
Xiaoting ZHANG
1
;
Jingyu ZHANG
1
;
Lianjie PENG
1
;
Yaxian LUO
1
;
Lining LIN
1
;
Yiting LOU
1
;
Dongqi YOU
1
;
Tao QIU
1
;
Zhichao LIU
1
;
Qianting WANG
1
;
Yu LIU
2
;
Ping SUN
3
;
Mengfei YU
4
;
Huiming WANG
1
Author Information
1. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China.
2. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China. 7514061@zju.edu.cn.
3. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China. nosleep@zju.edu.cn.
4. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China. yumengfei@zju.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Humans;
MicroRNAs/metabolism*;
RNA, Long Noncoding/metabolism*;
Head and Neck Neoplasms/metabolism*;
Cell Proliferation;
Squamous Cell Carcinoma of Head and Neck/genetics*;
Urokinase-Type Plasminogen Activator/genetics*;
Cell Movement;
Cell Line, Tumor;
Gene Expression Regulation, Neoplastic;
Carcinoma, Squamous Cell/genetics*;
Neoplasm Invasiveness
- From:
International Journal of Oral Science
2024;16(1):63-63
- CountryChina
- Language:English
-
Abstract:
The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
