M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Abstract

Background: Growing studies have focused on the role of microRNA-21 (miR-21) in glioma, thus our objective was to discuss the effect of M2 bone marrow-derived macrophage (BMDM)-derived exosomes (BMDM-Exos) shuffle miR-21 on biological functions of glioma cells by regulating paternally expressed gene 3 (PEG3). Methods: Seventy-one cases of human glioma tissues and 30 cases of non-tumor normal brain tissues were collected and stored in liquid nitrogen. PEG3 and miR-21 expression in glioma tissues was tested. The fasting venous blood of glioma patients and healthy control was collected and centrifuged, and then the supernatant was stored at − 80 °C refrigerator. The contents of interferon (IFN)-γ and transforming growth factor-β1 (TGF-β1) in serum were tested by ELISA. Glioma cells and normal glial cells were cultured to screen the target cells for further in vitro experiments. BMDM-Exos was obtained by ultra-high speed centrifugation and then was identified. BMDM-Exos was cocultured with U87 cells to detect the biological functions. The fasting venous blood of glioma patients was extracted and treated with ethylene diamine tetraacetic acid-K2 anti-freezing, and then CD8 + T cells were isolated. CD8 + T cells were co-cultured with U87 cells to detect the CD8 + T proliferation, cell cytotoxic activity, U87 cell activity, as well as IFN-γ and TGF-β1 levels. Moreover, BALB/c-nu/nu mice was taken, and the human-nude mouse glioma orthotopic transplantation model was established with U87 cells, and then mice were grouped to test the trends in tumor growth. The brain of mice (fixed by 10% formaldehyde) was sliced to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The spleen of mice was taken to prepare single-cell suspension, and the percentage of T lymphocytes in spleen to CD8 + T cells was detected. Results: PEG3 expression was decreased and miR-21 expression was increased in glioma cells and tissues. Depleting miR-21 or restoring PEG3 suppressed growth, migration and invasion as well as accelerated apoptosis of glioma cells, also raised CD8 + T proliferation, cell cytotoxic activity, and IFN-γ level as well as decreased U87 cell activity and TGF-β1 level. BMDM-Exos shuttle miR-21 promoted migration, proliferation and invasion as well as suppressed apoptosis of glioma cells by reducing PEG3. Exosomes enhanced the volume of tumor, Ki67 and PCNA expression, reduced the percentage of CD8 + T cells in glioma mice.

Immune-Related Four-lncRNA Signature for Patients with Cervical Cancer

“…Additionally, ZNF667-AS1 can competitively bind to miR-93-3p, which targets PEG3, to regulate the progression of CC [ 31 ]. Recent research has shown that inhibiting PEG3 would promote the immune escape of cancer cells [ 32 ]. BZRAP1-AS1 was found to be a novel biomarker associated with prostate cancer (PC), being downregulated in PC samples [ 33 ].…”

Exosome-mediated communication between tumor cells and tumor-associated macrophages: implications for tumor microenvironment

“…TAMs suppress the CD8 + T cell response to cancer by secreting immunosuppressive factors, including CCL5, CCL17, and CCL22. 132 In addition to these chemokines, Yang et al 133 found that M2-BMDM-derived exosomes (BMDM-Exos) shuttle miR-21 to promote migration, proliferation, and invasion, and inhibit the apoptosis of glioma cells by reducing the expression of paternally expressed gene 3 (PEG3). More importantly, this work provided evidence that BMDM-Exos can reduce the percentage of CD8 + T cells and inhibit the extent of cell cytotoxicity by accelerating the immune escape of gliomas and enhancing their progression.…”

Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer

“…Additionally, ZNF667-AS1 can competitively bind to miR-93-3p, which targets PEG3, to regulate the progression of CC [31]. Recent research has shown that inhibiting PEG3 would promote the immune escape of cancer cells [32]. BZRAP1-AS1 was found to be a novel biomarker associated with prostate cancer(PC), being down-regulated in PC samples [33].…”