Tumor-Derived EBV-miR-BART2-5p Promotes Nasopharyngeal Carcinoma Metastasis by Inducing Premetastatic Endothelial Cell Pyroptosis

Extravasation is a key step in tumor metastasis. Epstein‒Barr virus plays a crucial role in nasopharyngeal carcinoma (NPC) metastasis. However, the functions and molecular mechanisms of Epstein‒Barr virus during tumor cell extravasation remain unclear. Here, we showed that the expression of pyroptosis-associated proteins is greater in the endothelial cells of metastatic NPC tissues than in those of nontumor tissues exosomes derived from NPC cells promoted endothelial cell pyroptosis, vascular permeability, and tumor cell extravasation. Moreover, we found that BART2-5p is abundant in serum exosomes from patients with NPC metastasis and in NPC cells and that it regulates endothelial cell pyroptosis in premetastatic organs via MRE11A. Exosomes containing a BART2-5p inhibitor and AAV-MRE11A attenuated endothelial cell pyroptosis and tumor metastasis. Moreover, in the endothelial cells of metastatic tissues from patients with NPC, the BART2-5p level was positively associated with pyroptosis-related protein expression. Collectively, our findings suggest that exosomal BART2-5p is involved in premetastatic niche formation, identifying secreted BART2-5p as a potential therapeutic target for NPC metastasis. Implications: The finding that secreted BART2-5p is involved in premetastatic niche formation may aid the development of a potential therapeutic target for NPC metastasis.

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Journal
Molecular Cancer Research
Published
2024-11-15
DOI
https://doi.org/10.1158/1541-7786.mcr-24-0165
Citations
2
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
0.47
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article

Tumor-Derived EBV-miR-BART2-5p Promotes Nasopharyngeal Carcinoma Metastasis by Inducing Premetastatic Endothelial Cell Pyroptosis

Qianbing Zhang, Dengke Li, Xiaoming Lyu, Zhongxi Huang et al.
2 citations
Molecular Cancer Research
Extracellular vesicles in disease
0.47
article

Tumor-Derived EBV-miR-BART2-5p Promotes Nasopharyngeal Carcinoma Metastasis by Inducing Premetastatic Endothelial Cell Pyroptosis

Qianbing Zhang, Dengke Li, Xiaoming Lyu, Zhongxi Huang, Jun Deng, Kai‐Tai Yao, Jike Li, Linbo Cai, Jiangyu Zhang, Xin Li, Jiahong Wang, Qiqi Li, Xiaoyan Fu, Liang Chen, Mengying Qiu, Hainan Li, Xingrui Chen
article en
2 citations

Abstract

Extravasation is a key step in tumor metastasis. Epstein‒Barr virus plays a crucial role in nasopharyngeal carcinoma (NPC) metastasis. However, the functions and molecular mechanisms of Epstein‒Barr virus during tumor cell extravasation remain unclear. Here, we showed that the expression of pyroptosis-associated proteins is greater in the endothelial cells of metastatic NPC tissues than in those of nontumor tissues exosomes derived from NPC cells promoted endothelial cell pyroptosis, vascular permeability, and tumor cell extravasation. Moreover, we found that BART2-5p is abundant in serum exosomes from patients with NPC metastasis and in NPC cells and that it regulates endothelial cell pyroptosis in premetastatic organs via MRE11A. Exosomes containing a BART2-5p inhibitor and AAV-MRE11A attenuated endothelial cell pyroptosis and tumor metastasis. Moreover, in the endothelial cells of metastatic tissues from patients with NPC, the BART2-5p level was positively associated with pyroptosis-related protein expression. Collectively, our findings suggest that exosomal BART2-5p is involved in premetastatic niche formation, identifying secreted BART2-5p as a potential therapeutic target for NPC metastasis. Implications: The finding that secreted BART2-5p is involved in premetastatic niche formation may aid the development of a potential therapeutic target for NPC metastasis.

Molecular Cancer ResearchVol. 23(3)
Sun Yat-sen University (CN), Third Affiliated Hospital of Southern Medical University (CN), Sixth Affiliated Hospital of Sun Yat-sen University (CN), General Hospital of Guangzhou Military Command (CN), Guangdong Institute for Drug Control (CN), Southern Medical University Shenzhen Hospital (CN), Guangdong Province Women and Children Hospital (CN), Shanghai Sixth People's Hospital (CN), Guangzhou Medical University Cancer Hospital (CN), Guangdong 999 Brain Hospital (CN), Southern Medical University (CN), Guangzhou Medical University (CN)
Good health and well-being
Openalex Percentile: Top 34%
Extracellular vesicles in disease
0.47
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