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

Exosome-derived miR-20a inhibit apoptosis of TAM by targeting BCL2L11 in nasopharyngeal carcinoma

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BCL2L11,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。

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-20 aexpression by qRT-PCR.Furthermore,apoptosis index and proteins involved in apoptotic pathways were detected after miR-20 amimic and inhibitor transfection into macrophages.Results miR-20 aexpression was upregulated in isolated exosomes.miR-20 atarget gene was BCL2L11.MiR-20 aoverexpression could inhibit apoptosis of macrophages,meanwhile,apoptotic pathways related proteins Bim,caspase-9and caspase-3were significantly suppressed by miR-20amimic（P〈0.05）.Conclusion miR-20 acan suppress activation of Bim-caspase-9-casepase-3and resulting in apoptotic inhibition of macrophages.