Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis
| Autor: | 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, Xu Yang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 22, Iss, Pp 153-165 (2020) |
| ISSN: | 2162-2531 |
| DOI: | 10.1016/j.omtn.2020.08.017 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|