Exosome Linc00665 regulates radiotherapy resistance in oral squamous cell carcinoma by regulating T cell immunoreactivity
10.3969/j.issn.1001-3733.2025.06.003
- VernacularTitle:外泌体Linc00665调控T细胞免疫活性促进口腔鳞癌放疗抵抗的作用机制研究
- Author:
Huan LI
1
;
Junhong HUANG
1
;
Yating HU
1
;
Yahui LI
1
;
Zihui YANG
1
;
Zhenyan ZHAO
1
;
Xinjie YANG
1
;
Jianhua WEI
1
Author Information
1. 710032 西安,口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔疾病临床医学研究中心,空军军医大学口腔医院颌面肿瘤科
- Publication Type:Journal Article
- Keywords:
Oral squamous carcinoma;
Radiotherapy resistance;
Linc00665;
Exosome
- From:
Journal of Practical Stomatology
2025;41(6):744-749
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the function and mechanism of exosome Linc00665 in modulating CD8+T cell immunoreactivity to promote radiotherapy resistance in OSCC.Methods:HOEC,SCC9 and SCC9-RR exosomes were extracted and identified,and the expression of Linc00665 was detected by qRT-PCR in cell lines and exosomes.The expression of TNF-α,IFN-γ,perforin and granzyme B in each treatment group was detected by ELISA(PBS,SCC9 exo,SCC9-RR exo).The killing ability of CD8+T cells against SCC9 cells in each treatment group was detected by CCK-8 assay.The targets of Linc00665 were further bioinformatically ana-lyzed and verified by qRT-PCR and Western blot.The expression of Linc00665,miR-28-5p and PD-1 in CD8+T cells was exogenous-ly regulated,the expression of immunoreactive factors in the supernatants of each treatment group was detected by ELISA(NC,sh-Linc00665,miR-28-5p inhibitor,sh-PD-1),and the killing ability of cells in each group was detected by CCK-8 method.Results:The concentrations of TNF-α,IFN-γ,perforin and granzyme B in the supernatants of cell culture in the SCC9-RR exo/CD8+T group were significantly decreased compared with those in the PBS/CD8+T group and the SCC9 exo/CD8+T group(P＜0.05),and the kill-ing ability of the cells in the SCC9-RR exo group was significantly decreased compared with those in the PBS group and the SCC9 exo group(P＜0.05),suggesting that SCC9-RR exo could inhibit the tumor killing ability of CD8+T cells.qRT-PCR results suggested that Linc00665 was highly expressed in the SCC9-RR cell line as well as exosome(P＜0.05).It was further verified by bioinformat-ics analysis that Linc00665 could regulate PD-1 expression via miR-28-5p,thereby modulating CD8+T cell immunoreactivity to pro-mote OSCC radiotherapy resistance.Conclusion:Exosome Linc00665 regulates CD8+T cell immunoreactivity through miR-28-5p/PD-1 axis to promote OSCC radiotherapy resistance.
