circ_0101145 promotes immune escape of gastric cancer cells through miR-548c-3p/PD-L1 axis
10.3969/j.issn.1000-484X.2025.01.013
- VernacularTitle:circ_0101145通过miR-548c-3p/PD-L1轴促进胃癌细胞的免疫逃逸
- Author:
Can WANG
1
;
Xianmo YANG
;
Hai LIU
Author Information
1. 遵义市第一人民医院胃肠外科,遵义 564700
- Publication Type:Journal Article
- Keywords:
circ_0101145;
miR-548c-3p;
Programmed death-ligand 1;
Gastric cancer;
Immune escape
- From:
Chinese Journal of Immunology
2025;41(1):85-92
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of circ_0101145 on immune escape of gastric cancer(GC)cells through miR-548c-3p/programmed death-ligand 1(PD-L1)axis.Methods:RT-qPCR and Western blot were used to detect circ_0101145,miR-548c-3p,PD-L1 mRNA and protein levels in GC tissue and cell lines,the relationship between circ_0101145 level and clinical patho-logical parameters of patients was analyzed;dual Luciferase experiment was used to verify the regulatory relationship of circ_0101145 on miR-548c-3p,miR-548c-3p on PD-L1;liposome transfection method was used to structure BGC-823 transfected cell line,divided into circ-NC group,circ_0101145 group,si-circ-NC group,si-circ_0101145 group,circ_0101145+NC group,circ_0101145+miR-548c-3p group,miR-548c-3p+NC group,miR-548c-3p+PD-L1 group.CD8+T cells were separated from human peripheral blood and cocultivate with BGC-823 cell;flow cytometry was used to detect CD8+T cells apoptosis rate;ELISA was used to detect TNF-α,IFN-γ levels in coculture medium;CCK-8,EdU staining,Transwell assay were used to detect cell proliferation,invasion ability.Nude mice was subcutaneous inject with BGC-823 cell suspension of knockdown circ_0101145,after 30 days,growth of transplanted tumors were measured.Results:Compared with adjacent cancer tissues or normal cells,miR-548c-3p level in GC tissues and cell lines were de-creased,while circ_0101145,PD-L1 mRNA and protein levels were increased,and the higher circ_0101145 level,the higher TNM stage,the lower degree of tumor differentiation,the easier microvascular infiltration,and the easier lymph node metastasis(P<0.05);circ_0101145 targeted miR-548c-3p,miR-548c-3p targeted PD-L1.In the cocultivation system,overexpression of circ_0101145 could increase CD8+T cells apoptosis rate,and TNF-α,IFN-γ levels in coculture supernatant were reduced,the A value after 1 day,2 days and 3 days,EdU positive rate and the number of invasive cell were increased(P<0.05).Knock down of circ_0101145 could de-crease the apoptosis rate of CD8+T cells,and TNF-α,IFN-γ levels in coculture supernatant were increased;the A value after 1 day,2 days and 3 days,EdU positive rate and the number of invasive cell were decreased(P<0.05).Overexpression of miR-548c-3p could partially reverse the effect of overexpression of circ_0101145 on the above indicators(P<0.05).Overexpression of PD-L1 could partially reverse the effect of overexpression of miR-548c-3p on the above indicators(P<0.05).Knock down of circ_0101145 could inhibit the growth of transplanted tumors in mice(P<0.05).Conclusion:circ_0101145 promotes immune escape of GC cells through miR-548c-3p/PD-1 axis.
