The miR-192/EGR1-HOXB9 loop inhibits immune evasion in glioma by arresting their NSC phenotypes.

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Tác giả: Yan-Ping Jin, Guo-Wei Li, Min-Feng Sheng

Ngôn ngữ: eng

Ký hiệu phân loại: 332.34 Pawnshops

Thông tin xuất bản: Netherlands : International immunopharmacology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 718352

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.
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