Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in mac-rophage through PTEN/AKT signaling pathway
10.12016/j.issn.2096-1456.2024.01.003
- VernacularTitle: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
- Author:
Pengfei JIAO
1
,
2
,
3
;
Zeyu WANG
;
Heming WU
;
Si-Yue YAO
;
Huilin WANG
;
Enhui YAO
;
Yuyao ZHANG
;
Yi YUAN
;
Yi ZHONG
Author Information
1. 苏州市卫生职业技术学院附属苏州市华夏口腔医院,江苏 苏州(215000)
2. 江苏省口腔疾病研究重点实验室,江苏 南京(210029)
3. 江苏省口腔转化医学工程研究中心,江苏 南京(210029)
- Keywords:
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
- From:
Journal of Prevention and Treatment for Stomatological Diseases
2024;32(1):12-21
- CountryChina
- Language:Chinese
-
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.
