Tumor-Derived EV-Encapsulated miR-181b-5p Induces Angiogenesis to Foster Tumorigenesis and Metastasis of ESCC

Molecular Therapy: Nucleic Acids

Huan Bian¹  Jiqiang Lu¹  Dongping Li¹  Hanmei Xu¹  Lin Chen²  Jialiang Hu²  Ying Wang²  Chunlei Xia² 

[1] State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China;The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing 210009, China;

关键词: angiogenesis;    extracellular vesicle;    miR-181b-5p;    metastasis;    prognosis;    esophageal squamous cell carcinoma;   

DOI  :  

来源: DOAJ

【 摘 要 】

Pathological angiogenesis is necessary for tumor development and metastasis. Tumor-derived extracellular vesicles (EVs) play an important role in mediating the crosstalk between cancer cells and vascular endothelial cells. To date, whether and how microRNAs (miRNAs) encapsulated in tumor-derived EVs affect angiogenesis in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that miR-181b-5p, an angiogenesis-promoting miRNA of ESCC, can be transferred from ESCC cells to vascular endothelial cells via EVs. In addition, ESCC-derived EVs-miR-181b-5p dramatically induced angiogenesis by targeting PTEN and PHLPP2, and thereby facilitated tumor growth and metastasis. Moreover, miR-181b-5p was highly expressed in ESCC tissues and serum EVs. High miR-181b-5p expression level in ESCC patients was well predicted for poor overall survival. Our work suggests that intercellular crosstalk between tumor cells and vascular endothelial cells is mediated by tumor-derived EVs. miR-181b-5p-enriched EVs secreted from ESCC cells are involved in angiogenesis that control metastasis of ESCC, providing a potential diagnostic biomarker or drug target for ESCC patients.

【 授权许可】

Unknown