{"title":"敲低circ_0000372通过海绵miR-488-3p提高PD-L1水平，抑制胃癌细胞活力、运动和免疫逃逸","authors":"Chao Shen, Wei Li, Ji Shi, Yan Wu, Yichao Yan","doi":"10.1007/s10735-025-10598-x","DOIUrl":null,"url":null,"abstract":"<div><p>Gastric cancer (GC) development is influenced by crosstalk between tumor cells and host immune elements. Circ_0000372 has potential as an oncogene. This research aimed to investigate the circ_0000372 mechanism in GC. Circ_0000372 expressions were evaluated via the GSE194384 database. The overall survival of GC patients was determined via the Kaplan-Meier Survival Curve. Gene relationships were assessed using the Chi-square test. Circ_0000372 functions in GC were evaluated with qRT-PCR, Cell Counting Kit-8 analysis, 5-ethynyl-2’-deoxyuridine analysis, Transwell, Western blot, co-culture of peripheral blood mononuclear cells (PBMCs) and GC cells, flow cytometry, and ELISA. Meanwhile, the circ_0000372 mechanism was examined by RNA pull-down, dual-luciferase reporter assay, and Spearman Correlation Analysis. Finally, the circ_0000372 impact <i>on</i> tumor-bearing mice was analyzed by immunohistochemistry and western blot assays. Elevated circ_0000372 levels were detected in GC. Patients with raised circ_0000372 levels had a poor prognosis. Besides, circ_0000372 expressions were interrelated to TNM stage and lymph node metastasis. Silencing circ_0000372 repressed GC cell proliferation and invasion. Silencing circ_0000372 reduced immune escape with reduced PD-L1 protein levels and increased CD8 + T cell percentage. Moreover, circ_0000372 positively regulated PD-L1 expression via miR-488-3p, and circ_0000372 knockdown restrained GC cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p. The interference of circ_0000372 also reduced GC tumor formation, tumor weight, and PD-L1 level with elevated IFN-γ level in vivo. A high circ_0000372 level indicated a GC poor prognosis. Silencing circ_0000372 suppressed cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Mode pattern of circ_0000372/miR-488-3p/PD-L1 in mediating GC cell proliferation, invasion, immune escape</p></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Knockdown of circ_0000372 elevates PD-L1 level through sponging miR-488-3p to restrain cell viability, motility and immune escape in gastric cancer\",\"authors\":\"Chao Shen, Wei Li, Ji Shi, Yan Wu, Yichao Yan\",\"doi\":\"10.1007/s10735-025-10598-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Gastric cancer (GC) development is influenced by crosstalk between tumor cells and host immune elements. Circ_0000372 has potential as an oncogene. This research aimed to investigate the circ_0000372 mechanism in GC. Circ_0000372 expressions were evaluated via the GSE194384 database. The overall survival of GC patients was determined via the Kaplan-Meier Survival Curve. Gene relationships were assessed using the Chi-square test. Circ_0000372 functions in GC were evaluated with qRT-PCR, Cell Counting Kit-8 analysis, 5-ethynyl-2’-deoxyuridine analysis, Transwell, Western blot, co-culture of peripheral blood mononuclear cells (PBMCs) and GC cells, flow cytometry, and ELISA. Meanwhile, the circ_0000372 mechanism was examined by RNA pull-down, dual-luciferase reporter assay, and Spearman Correlation Analysis. Finally, the circ_0000372 impact <i>on</i> tumor-bearing mice was analyzed by immunohistochemistry and western blot assays. Elevated circ_0000372 levels were detected in GC. Patients with raised circ_0000372 levels had a poor prognosis. Besides, circ_0000372 expressions were interrelated to TNM stage and lymph node metastasis. Silencing circ_0000372 repressed GC cell proliferation and invasion. Silencing circ_0000372 reduced immune escape with reduced PD-L1 protein levels and increased CD8 + T cell percentage. Moreover, circ_0000372 positively regulated PD-L1 expression via miR-488-3p, and circ_0000372 knockdown restrained GC cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p. The interference of circ_0000372 also reduced GC tumor formation, tumor weight, and PD-L1 level with elevated IFN-γ level in vivo. A high circ_0000372 level indicated a GC poor prognosis. Silencing circ_0000372 suppressed cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Mode pattern of circ_0000372/miR-488-3p/PD-L1 in mediating GC cell proliferation, invasion, immune escape</p></div></div></figure></div></div>\",\"PeriodicalId\":650,\"journal\":{\"name\":\"Journal of Molecular Histology\",\"volume\":\"56 5\",\"pages\":\"\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Histology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10735-025-10598-x\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Histology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10735-025-10598-x","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Knockdown of circ_0000372 elevates PD-L1 level through sponging miR-488-3p to restrain cell viability, motility and immune escape in gastric cancer
Gastric cancer (GC) development is influenced by crosstalk between tumor cells and host immune elements. Circ_0000372 has potential as an oncogene. This research aimed to investigate the circ_0000372 mechanism in GC. Circ_0000372 expressions were evaluated via the GSE194384 database. The overall survival of GC patients was determined via the Kaplan-Meier Survival Curve. Gene relationships were assessed using the Chi-square test. Circ_0000372 functions in GC were evaluated with qRT-PCR, Cell Counting Kit-8 analysis, 5-ethynyl-2’-deoxyuridine analysis, Transwell, Western blot, co-culture of peripheral blood mononuclear cells (PBMCs) and GC cells, flow cytometry, and ELISA. Meanwhile, the circ_0000372 mechanism was examined by RNA pull-down, dual-luciferase reporter assay, and Spearman Correlation Analysis. Finally, the circ_0000372 impact on tumor-bearing mice was analyzed by immunohistochemistry and western blot assays. Elevated circ_0000372 levels were detected in GC. Patients with raised circ_0000372 levels had a poor prognosis. Besides, circ_0000372 expressions were interrelated to TNM stage and lymph node metastasis. Silencing circ_0000372 repressed GC cell proliferation and invasion. Silencing circ_0000372 reduced immune escape with reduced PD-L1 protein levels and increased CD8 + T cell percentage. Moreover, circ_0000372 positively regulated PD-L1 expression via miR-488-3p, and circ_0000372 knockdown restrained GC cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p. The interference of circ_0000372 also reduced GC tumor formation, tumor weight, and PD-L1 level with elevated IFN-γ level in vivo. A high circ_0000372 level indicated a GC poor prognosis. Silencing circ_0000372 suppressed cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p.
Graphical abstract
Mode pattern of circ_0000372/miR-488-3p/PD-L1 in mediating GC cell proliferation, invasion, immune escape
期刊介绍：
The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes.
Major research themes of particular interest include:
- Cell-Cell and Cell-Matrix Interactions;
- Connective Tissues;
- Development and Disease;
- Neuroscience.
Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance.
The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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