鼻咽癌外泌体miR-20a通过靶向BCL2L11基因抑制肿瘤相关巨噬细胞凋亡

摘要

Objective To investigate whether exosome-derived microRNA of nasopharyngeal carcinoma suppresses apoptosis of tumor associated macrophage (TAM).Methods Target microRNAs and genes were determined by bioinformatics methods.Isolated exosomes were used to detect miR-20a expression by qRT-PCR.Furthermore,apoptosis index and proteins involved in apoptotic pathways were detected after miR-20a mimic and inhibitor transfection into macrophages.Results miR-20a expression was upregulated in isolated exosomes.miR-20a target gene was BCL2L11.MiR-20a overexpression could inhibit apoptosis of macrophages,meanwhile,apoptotic pathways related proteins Bim,caspase-9 and caspase-3 were significantly suppressed by miR-20a mimic(P＜0.05).Condusion miR-20a can suppress activation of Bim-caspase-9-casepase-3 and resulting in apoptotic inhibition of macrophages.%目的 探索鼻咽癌外泌体microRNA是否通过靶向凋亡基因而抑制肿瘤相关巨噬细胞(TAM)凋亡.方法 通过生物信息学方法确定目标microRNA及其靶基因,检测鼻咽癌患者血清及鼻咽癌细胞培养基中的外泌体内miR-20a的表达量.应用miR-20a的拟似物及抑制物转染巨噬细胞;并检测干预后的凋亡指数及凋亡通路相关蛋白.结果 miR-20a在鼻咽癌外泌体中表达显著上调.miR-20a的靶基因为BCL2 L11,过表达miR-20a可以抑制巨噬细胞凋亡,且凋亡通路相关蛋白Bim、caspase-9和caspase-3均显著减少(P＜0.05).结论 miR-20a通过抑制Bim-caspase-9-caspase-3凋亡途径的活化从而抑制鼻咽癌中TAM凋亡.