{"title":"The miR-192/EGR1-HOXB9 loop inhibits immune evasion in glioma by arresting their NSC phenotypes","authors":"Guo-Wei Li , Yan-Ping Jin , Min-Feng Sheng","doi":"10.1016/j.intimp.2025.114453","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>To elucidate the mechanism by which the miR-192-related axis regulates glioma immune evasion.</div></div><div><h3>Methods</h3><div>Factor expression was measured by PCR/Western Blotting (WB). Immunofluorescence, FISH and DLRTM were used to elucidate target regulation mechanisms. Mitophagy was observed by TEM. We performed BrdU/Transwell assays to evaluate malignant phenotypes and WB to measure stemness-related protein expression in glioma. Immune chemokine levels were measured by ELISA, and M2-TAM/CD8+ T-cell proportions were measured by immune-fluorescence. Growth curves/tumor volume in vivo and tumor weight in vitro were assessed to evaluate tumor growth in vivo. An immune microenvironment was established in nude mice via tail vein injection of immune cells. Masson's trichrome staining was performed to explore the degree of fibrosis in relevant tissues.</div></div><div><h3>Results</h3><div>MiR-192 expression was negatively correlated with glioma malignancy. The expression of downstream regulator (EGR1/HOXB9) of miR-192 was positively correlated with malignant phenotypes. MiR-192 inhibited EGR1/HOXB9 through targeted binding. The miR-192/EGR1-HOXB9 loop induced mitophagy, thus inhibited glioma cell proliferation/invasion. Moreover, this loop inhibited MT, weakening glioma cell stemness. This pathway reduced M2-TAM numbers and weakened their inhibitory effect on CD8+ T-cells by regulating immune chemokines. In vivo, miR-192 inhibited glioma proliferation and induced immune infiltration into glioma through this loop.</div></div><div><h3>Conclusion</h3><div>The miR-192/EGR1-HOXB9 loop inhibited glioma stemness phenotypes, weakening glioma malignancy by regulating mitophagy. Moreover, this loop affected chemokine secretion by TAMs, weakened their inhibitory effect on CD8+ T-cells and reduced immune evasion in glioma by regulating MT.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114453"},"PeriodicalIF":4.8000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925004436","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
To elucidate the mechanism by which the miR-192-related axis regulates glioma immune evasion.
Methods
Factor expression was measured by PCR/Western Blotting (WB). Immunofluorescence, FISH and DLRTM were used to elucidate target regulation mechanisms. Mitophagy was observed by TEM. We performed BrdU/Transwell assays to evaluate malignant phenotypes and WB to measure stemness-related protein expression in glioma. Immune chemokine levels were measured by ELISA, and M2-TAM/CD8+ T-cell proportions were measured by immune-fluorescence. Growth curves/tumor volume in vivo and tumor weight in vitro were assessed to evaluate tumor growth in vivo. An immune microenvironment was established in nude mice via tail vein injection of immune cells. Masson's trichrome staining was performed to explore the degree of fibrosis in relevant tissues.
Results
MiR-192 expression was negatively correlated with glioma malignancy. The expression of downstream regulator (EGR1/HOXB9) of miR-192 was positively correlated with malignant phenotypes. MiR-192 inhibited EGR1/HOXB9 through targeted binding. The miR-192/EGR1-HOXB9 loop induced mitophagy, thus inhibited glioma cell proliferation/invasion. Moreover, this loop inhibited MT, weakening glioma cell stemness. This pathway reduced M2-TAM numbers and weakened their inhibitory effect on CD8+ T-cells by regulating immune chemokines. In vivo, miR-192 inhibited glioma proliferation and induced immune infiltration into glioma through this loop.
Conclusion
The miR-192/EGR1-HOXB9 loop inhibited glioma stemness phenotypes, weakening glioma malignancy by regulating mitophagy. Moreover, this loop affected chemokine secretion by TAMs, weakened their inhibitory effect on CD8+ T-cells and reduced immune evasion in glioma by regulating MT.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.