口腔疾病防治2024，Vol.32Issue(1)：12-21,10.DOI:10.12016/j.issn.2096-1456.2024.01.003
内质网应激头颈部鳞状细胞癌细胞通过外泌体miR-26a-5p调控PTEN/AKT通路促进巨噬细胞PD-L1表达
Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in mac-rophage through PTEN/AKT signaling pathway
摘要
Abstract
Objective To investigate the impact of exosomal miRNAs derived from endoplasmic reticulum-stressed(ERS)head and neck squamous cell carcinoma(HNSCC)cells on macrophages.Methods This study was reviewed and approved by the Ethics Committee.The expression levels of ERS-associated proteins,including protein kinase R-like endoplasmic reticulum kinase(PERK)and glucose-regulated protein 78(GRP78),in HNSCC tissues and para-tumor tissues were detected by Western blot(WB)and quantitative real-time PCR(RT-qPCR).HN4 human laryngeal squamous cell carcinoma cells were treated with 500 U/mL interferon-γ(IFN-γ)for 48 h to induce ER stress,and exo-somes secreted by ER-stressed HN4 cells were collected and identified.The types of miRNAs in exosomes were identi-fied through bioinformatics analysis,and the target genes of miRNAs were predicted.Macrophages were transfected with miRNA,co cultured with collected exosomes,and the expression of PTEN in macrophages was knocked down.The downstream signaling pathway regulated by exosomal miRNAs was studied by WB and RT-qPCR.Results Compared with that in para-tumor tissues,the expression level of ER stress-associated proteins in HNSCC tissues was increased(P＜0.05).RNA-seq analysis revealed that miR-26a-5p was highly upregulated in ER-stressed HN4 cell-derived exo-somes(P＜0.05).PTEN is the target gene for miR-26a-5p.miR-26a-5p increased the expression level of PD-L1 in mac-rophages and downregulated the expression of PTEN(P＜0.05).Macrophages co cultured with ERS extracellular vesi-cles showed an increase in miR-26a-5p and PD-L1 expression,a decrease in PTEN expression,and an increase in p-AKT expression(P＜0.05).Knock down the expression of PTEN in macrophages and increase the expression of PD-L1(P＜0.01).Conclusion ERS HNSCC cell-derived exosomal miR-26a-5p promotes the expression of PD-L1 in macro-phages through the PTEN/AKT signaling pathway.关键词
头颈部鳞状细胞癌/内质网应激/miR-26a-5p/外泌体/巨噬细胞/程序性死亡受体-1配体/蛋白酪氨酸磷酸酶/蛋白激酶BKey words
head and neck squamous cell carcinoma/endoplasmic reticulum stress/exosome/miR-26a-5p/macrophage/programmed death receptor ligand 1/phosphate and tension homology deleted on chromsome ten/pro-tein kinase B分类
医药卫生引用本文复制引用
焦鹏飞,王泽宇,武和明,姚思玥,王慧琳,姚恩惠,张雨垚,袁毅,钟旖..内质网应激头颈部鳞状细胞癌细胞通过外泌体miR-26a-5p调控PTEN/AKT通路促进巨噬细胞PD-L1表达[J].口腔疾病防治,2024,32(1):12-21,10.基金项目
国家自然科学青年基金项目(82203580) （82203580）
江苏省卫健委医学科研项目(M2020003)This study was supported by the grants from National Nature Science Foundation of China(No.82203580)and the Health Committee of Jiangsu Province(No.M2020003). （M2020003）
