Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10

• Published in: Oncogene Vol. 37; no. 21; pp. 2873 - 2889
• Main Authors: Bao, Lili, You, Bo, Shi, Si, Shan, Ying, Zhang, Qicheng, Yue, Huijun, Zhang, Jie, Zhang, Wei, Shi, Yunwei, Liu, Yifei, Wang, Xin, Liu, Dong, You, Yiwen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2018; Nature Publishing Group
• Subjects: 13/1; 13/105; 13/109; 13/2; 13/31; 13/51; 13/89; 14/19; 14/28; 631/67/1536; 631/67/322; 64/116; 64/60; Angiogenesis; Animals; Apoptosis; Cell Biology; Cell Line, Tumor; Cell organelles; Cell Proliferation; Development and progression; Disease Progression; Exosomes; Exosomes - genetics; Exosomes - pathology; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Human Genetics; Human Umbilical Vein Endothelial Cells; Humans; Internal Medicine; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice; MicroRNA; MicroRNAs - genetics; miRNA; Nasopharyngeal cancer; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Neoplasm Metastasis; Neovascularization; Neovascularization, Pathologic - genetics; Nutrients; Oncology; Physiological aspects; Proteins - genetics; Radiation therapy; Throat cancer; Up-Regulation; Zebrafish; China
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-018-0183-6

Benefiting from more precise imaging and radiotherapy, patients with locoregionally nasopharyngeal carcinoma (NPC) have a significantly higher survival rate. Nonetheless, distant metastasis is still the predominant mode of failure. Advances in cancer research have highlighted that pathological angiogenesis is necessary for tumor metastasis by offering oxygen, nutrients, or cell metastatic conduits. MicroRNAs (miRNAs), a class of small noncoding RNAs, are increasingly implicated in modulation of angiogenesis in physiological and pathological conditions. Currently, we detected that miR-23a was highly enriched in NPC tissues at the metastatic or premetastatic stage, and its levels in NPC were associated with microvessel density. Subsequently, we proved that alteration of miR-23a expression modulated the growth, migration, and tube formation of HUVECs in vitro and affected the blood vessel outgrowth in the zebrafish model. Considering the possibility that extracellular miR-23a was horizontally transferred from CNE2 cells to HUVECs, we analyzed miR-23a encapsulated in exosomes, showing that overexpression of exosomal miR-23a in NPC promoted angiogenesis both in vitro and in vivo. Moreover, we provided evidences that miR-23a regulated angiogenesis by directly targeting testis-specific gene antigen (TSGA10). Taken together, our findings revealed that metastasis-associated miR-23a from NPC-derived exosomes plays an important role in mediating angiogenesis by targeting TSGA10.