1. Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis
- Author
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Sai Wah Tsao, Hanzhao Li, Tuotuo Chong, Oluwasijibomi Damola Faleti, Min Zhao, Qiang Jiang, Xin Li, Yufei Long, Yuxiang Chen, Jianguo Wang, Tengteng Ding, Manli Peng, Yun-xi Cai, Yuanbin Zhang, Minyi Fu, Gongfa Wu, Chi Man Tsang, Xiaoming Lyu, and Xu Yang
- Subjects
0301 basic medicine ,Angiogenesis ,Biology ,Exosome ,law.invention ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,law ,Drug Discovery ,microRNA ,medicine ,exosome ,miRNA ,nasopharyngeal carcinoma ,lcsh:RM1-950 ,Cancer ,medicine.disease ,Microvesicles ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Suppressor ,Original Article ,antiangiogenesis - Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors., Graphical Abstract, Wang et al. generated a novel oncogenic pathway underlying angiogenesis regulation that involves EBV-miR-BART10-5p and hsa-miR-18a inhibiting tumor suppressor Spry3 and its downstream targets. They established a synergistic role between virus and host microRNAs in the regulation of angiogenesis of virus-associated cancer.
- Published
- 2020