首页|食管鳞状细胞癌外泌体miR-181b-5p通过靶向抑制PTEN促进肿瘤相关巨噬细胞极化

食管鳞状细胞癌外泌体miR-181b-5p通过靶向抑制PTEN促进肿瘤相关巨噬细胞极化

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目的:探究食管鳞状细胞癌外泌体miR-181b-5p对M2型巨噬细胞极化的影响及机制.方法:提取并鉴定食管鳞状细胞癌外泌体,qRT-PCR检测miR-181b-5p在食管鳞状癌细胞及其外泌体中的表达.M0型巨噬细胞分为PBS组、HEEC exo组、Eca-109 exo组、miR-NC exo组、miR-181b-5p exo组、miR-NC组、miR-181b-5p mimic组、si-NC组、si-PTEN组、miR-181b-5p exo+PTEN组,qRT-PCR检测各组细胞中CD163、CD206、iNOS、TNF-α表达.双荧光素酶报告基因实验验证miR-181b-5p和PTEN的靶向关系.结果:miR-181b-5p在食管鳞状癌细胞TE-13、TE-12、TE-10、Eca-109、KYSE30及其外泌体中显著高表达(P<0.001).相比于miR-NC组,miR-181b-5p mimic组细胞CD163和CD206表达显著上调(P<0.001),iNOS和TNF-α表达显著下调(P<0.001).双荧光素酶报告基因结果显示PTEN为miR-181b-5p的靶基因.相比于si-NC组,si-PTEN组细胞CD163和CD206表达显著上调(P<0.001),iNOS和TNF-α表达显著下调(P<0.001).相比于PBS组,Eca-109 exo组细胞CD163和CD206表达显著上调(P<0.001),而iNOS和TNF-α表达显著下调(P<0.001).相比于miR-NC exo组,miR-181b-5p exo组细胞CD163和CD206表达显著上调(P<0.001),而iNOS和TNF-α表达显著下调(P<0.001).相比于miR-181b-5p exo组,miR-181b-5p exo+PTEN组CD163和CD206表达显著下调(P<0.001),而iNOS和TNF-α表达显著上调(P<0.001).结论:外泌体miR-181b-5p抑制PTEN表达而促进M2型巨噬细胞极化.
Esophageal squamous cell carcinoma exosomal miR-181b-5p promotes tumor associated macrophage polarization by inhibiting PTEN
Objective:To investigate the effect and mechanism of esophageal squamous cell carcinoma exosomal miR-181b-5p to the polarization of M2 macrophages.Methods:Extracted and identified exosomes from esophageal squamous cell carcinoma,and detected the expression of miR-181b-5p in esophageal squamous cell carcinoma cells and their exosomes by qRT-PCR.M0 type macro-phages were divided into PBS group,HEEC exo group,Eca-109 exo group,miR-NC exo group,miR-181b-5p exo group,miR-NC group,miR-181b-5p mimic group,si-NC group,si-PTEN group,miR-181b-5p exo+PTEN group.qRT-PCR was used to detect the expressions of CD163,CD206,iNOS and TNF-α in each group.The targeting relationship between miR-181b-5p and PTEN were veri-fied by double luciferase reporter gene experiment.Results:miR-181b-5p was significantly overexpressed in esophageal squamous cell carcinoma cells TE-13,TE-12,TE-10,Eca-109,KYSE30 and their exosomes(P<0.001).Compared with miR-NC group,the expression of CD163 and CD206 in cells were significantly upregulated in the miR-181b-5p mimic group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).The results of double luciferase reporter genes showed that PTEN was the target gene of miR-181b-5p.Compared with si-NC group,the expressions of CD163 and CD206 in cells were significantly upregu-lated in the si-PTEN group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with PBS group,the expressions of CD163 and CD206 in cells were significantly upregulated in the Eca-109 exo group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with miR-NC exo group,the expressions of CD163 and CD206 in cells were significantly upregulated in the miR-181b-5p exo group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with miR-181b-5p exo group,the expressions of CD163 and CD206 in cells were significantly downregulated in the miR-181b-5p exo+PTEN group,as well as the expressions of iNOS and TNF-α were significantly upregulated(P<0.001).Conclusion:Exosomal miR-181b-5p inhibits PTEN expressions to promote M2 macrophage polarization.

Esophageal squamous cell carcinomaExosomesmiR-181b-5pMacrophagesPolarization

樊慧、赵乃阔、陈林林、李治国、柳淼、张远英、周超锋

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焦作市人民医院消化一区,焦作 454000

河南省中医院,河南中医药大学第二附属医院肿瘤内科,郑州 450000

食管鳞状细胞癌 外泌体 miR-181b-5p 巨噬细胞 极化

河南省科技攻关计划项目

202102310086

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(7)