外泌体来源的miR-181a促进胶质瘤的血管生成

Exosome-derived miR-181a promotes angiogenesis of glioma

目的:探讨外泌体来源的miR-181a对胶质瘤血管生成和肿瘤进展的影响。方法:选用2017年8月至2019年12月海南医学院第二附属医院手术切除的83例胶质瘤和13例瘤旁组织标本,以及胶质瘤细胞U87、A172、U251、LN229、U373和小神经胶质细胞HM,用qPCR法检测瘤组织和细胞中miR-181a的表达水平。构建过表达或敲减miR-181a的U373细胞,分离和鉴定外泌体;用小管形成实验、鸡胚绒毛尿囊膜血管实验观察外泌体来源的miR-181a对HUVEC小管和血管生成的影响。构建裸鼠U373细胞移植瘤模型,观察外泌体来源的miR-181a对血管生成及肿瘤生长的影响。结果:miR-181a在胶质瘤肿瘤组织和细胞中的表达水平明显高于瘤旁组织和HM细胞(均P<0.01)。外泌体来源的miR-181a可以明显促进HUVEC小管的形成和鸡胚尿绒毛囊膜的血管生成(均P<0.01)。裸鼠胶质细胞瘤体内实验发现,回输大量外泌体来源miR-181a的小鼠移植瘤进展更快(P<0.05)、肿瘤组织中血管生成数量显著增加(P<0.01)。结论:miR-181a在促进胶质瘤血管生成中发挥重要作用,可能成为胶质瘤诊断及治疗的潜在靶点。

Objective:To explore the effect of exosome-derived miR-181a on angiogenesis and tumor progression in gliomas.Methods:83 cases of glioma tissues and 13 cases of peritumoral tissues resected in the Second Affiliated Hospital of Hainan Medical University from August 2017 to December 2019,glioma cells U87,A172,U251,LN229,U373 and microglial cell line HM,were selected to detect the expression of miR-181a in tumor tissues and cells by qPCR method.Glioma U373 cells with miR-181a overexpression or knockdown were constructed,and exosomes were isolated and identified.The effects of exsome-derived miR-181a on angiogenesis of HUVEC cells were investigated by tubule formation and chicken chorioallantoic membrane assay in vitro.Nude mice bearing U373 cell transplanted xenograft was constructed to observe the effect of exsome-derived miR-181a on angiogenesis and tumor growth in vivo.Results:The expression of miR-181a in glioma tissues and cells was significantly higher than that in normal tissues and normal glial HM cells(all P<0.01).The exsome-derived miR-181a could significantly promote the tubule formation of HUVEC cells(P<0.01)and the angiogenesis of chicken chorioallantoic membrane(all P<0.01).In vivo experiments showed that the growth of xenografts was promoted(P<0.05)and the amount of angiogenesis in the tumor tissues was increased in the nude mice after being transfused with exsome-derived miR-181a(P<0.01).Conclusion:miR-181 a plays an important role in promoting angiogenesis of gliomas and may be a potential target for diagnosis and treatment of gliomas.