关键词: 食管鳞癌, 外泌体, miR-130a, 血管新生

Abstract: Objective To investigate the effect of miR-130a in esophageal squamous cell carcinoma exosomes on angiogenesis and its mechanism. Methods The exosomes secreted by esophageal epithelial cells HEEC, esophageal squamous cell carcinoma cells TE-13 and Eca-109, and transfected miR-130a mimic, miR-130a inhibitor and its negative control(NC) exosomes of Eca-109 cells were extracted, and co-incubated with human umbilical vein endothelial cells HUVEC. The proliferation, migration and tubule formation abilities of HUVEC cells in each group were detected by MTT, Transwell chamber and tubule formation experiments;  the expression level of miR-130a was detected by qRT-PCR;  the phosphorylation levels of PI3K and AKT as well as the expression levels of PTEN, Ang1 and iNOS were detected by Western blot. Results After HUVEC cells were co-incubated with TE-13 and Eca-109 cell exosomes, the proliferation, migration and tubule formation abilities were enhanced(P<0.01);  and the phosphorylation levels of PI3K and AKT and the expression levels of Ang1 and iNOS were up-regulated(P<0.001), while the expression level of PTEN was down-regulated(P<0.001). The qRT-PCR results showed that the expression level of miR-130a in TE-13 and Eca-109 cell exosomes were higher than that in HEEC exosomes(P<0.01). The down-regulation of miR-130a expression in Eca-109 cell exosomes could inhibit the proliferation, migration and tubule formation abilities of HUVEC cells(P＜0.01), while down-regulated the phosphorylation of PI3K and AKT and the expression levels of Ang1 and iNOS (P＜0.001), and up-regulated the expression level of PTEN(P<0.001). Conclusion The miR-130a in the exosomes of esophageal squamous cell carcinoma exosomes may induce tumor angiogenesis by activating the PTEN/PI3K/AKT signaling pathway of vascular endothelial cells.

Key words: Esophageal squamous cell carcinoma, Exosomes, miR-130a, Angiogenesis