Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway
Objective To investigate the impact of exosomal miRNAs derived from endoplasmic reticulum-stressed (ERS) head and neck squamous cell carcinoma (HNSCC) cells on macrophages. Methods This study was reviewed and approved by the Ethics Committee. The expression levels of ERS-associated proteins, includi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | zho |
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Editorial Department of Journal of Prevention and Treatment for Stomatological Diseases
2024-01-01
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| Series: | 口腔疾病防治 |
| Subjects: | |
| Online Access: | https://www.kqjbfz.com/CN/10.12016/j.issn.2096-1456.2024.01.003 |
| _version_ | 1797387724134547456 |
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| author | JIAO Pengfei WANG Zeyu WU Heming YAO Siyue WANG Huilin YAO Enhui ZHANG Yuyao YUAN Yi ZHONG Yi |
| author_facet | JIAO Pengfei WANG Zeyu WU Heming YAO Siyue WANG Huilin YAO Enhui ZHANG Yuyao YUAN Yi ZHONG Yi |
| author_sort | JIAO Pengfei |
| collection | DOAJ |
| description | Objective To investigate the impact of exosomal miRNAs derived from endoplasmic reticulum-stressed (ERS) head and neck squamous cell carcinoma (HNSCC) cells on macrophages. Methods This study was reviewed and approved by the Ethics Committee. The expression levels of ERS-associated proteins, including protein kinase R-like endoplasmic reticulum kinase (PERK) and glucose-regulated protein 78 (GRP78), in HNSCC tissues and para-tumor tissues were detected by Western blot (WB) and quantitative real-time PCR (RT-qPCR). HN4 human laryngeal squamous cell carcinoma cells were treated with 500 U/mL interferon-γ (IFN-γ) for 48 h to induce ER stress, and exosomes secreted by ER-stressed HN4 cells were collected and identified. The types of miRNAs in exosomes were identified through bioinformatics analysis, and the target genes of miRNAs were predicted. Macrophages were transfected with miRNA, co cultured with collected exosomes, and the expression of PTEN in macrophages was knocked down. The downstream signaling pathway regulated by exosomal miRNAs was studied by WB and RT-qPCR. Results Compared with that in para-tumor tissues, the expression level of ER stress-associated proteins in HNSCC tissues was increased (P<0.05). RNA-seq analysis revealed that miR-26a-5p was highly upregulated in ER-stressed HN4 cell-derived exosomes (P<0.05). PTEN is the target gene for miR-26a-5p. miR-26a-5p increased the expression level of PD-L1 in macrophages and downregulated the expression of PTEN (P<0.05). Macrophages co cultured with ERS extracellular vesicles showed an increase in miR-26a-5p and PD-L1 expression, a decrease in PTEN expression, and an increase in p-AKT expression (P<0.05). Knock down the expression of PTEN in macrophages and increase the expression of PD-L1 (P<0.01). Conclusion ERS HNSCC cell-derived exosomal miR-26a-5p promotes the expression of PD-L1 in macrophages through the PTEN/AKT signaling pathway. |
| first_indexed | 2024-03-08T22:29:13Z |
| format | Article |
| id | doaj.art-3a6a6ee9dded4a74b75597d9984db526 |
| institution | Directory Open Access Journal |
| issn | 2096-1456 |
| language | zho |
| last_indexed | 2024-03-08T22:29:13Z |
| publishDate | 2024-01-01 |
| publisher | Editorial Department of Journal of Prevention and Treatment for Stomatological Diseases |
| record_format | Article |
| series | 口腔疾病防治 |
| spelling | doaj.art-3a6a6ee9dded4a74b75597d9984db5262023-12-18T06:44:53ZzhoEditorial Department of Journal of Prevention and Treatment for Stomatological Diseases口腔疾病防治2096-14562024-01-01321122110.12016/j.issn.2096⁃1456.2024.01.003Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathwayJIAO Pengfei0WANG Zeyu1WU Heming2YAO Siyue3WANG Huilin4YAO Enhui5ZHANG Yuyao6YUAN Yi7ZHONG Yi81.The Affiliated Stomatology Hospital of Suzhou Vocational Health College.2.Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University 3.Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, School of Stomatology, Nanjing Medical University1Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University. 2.Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, School of Stomatology, Nanjing Medical University1.Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University 2.Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, School of Stomatology, Nanjing Medical University 3.Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Nanjing Medical University1.The Affiliated Stomatology Hospital of Suzhou Vocational Health College 2.Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University 3.Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, School of Stomatology, Nanjing Medical University1.Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University 2.Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, School of Stomatology, Nanjing Medical University1.Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University. 2.11.Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University 2.11.Jiangsu Province Key Laboratory of Oral Diseases, School of Stomatology, Nanjing Medical University 2.Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, School of Stomatology, Nanjing Medical University 3.Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Nanjing Medical University of Stomatology, Nanjing Medical University 2.Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, School of Stomatology, Nanjing Medical University 3.Department of Oral Pathology, the Affiliated Stomatological Hospital of Nanjing Medical UniversityObjective To investigate the impact of exosomal miRNAs derived from endoplasmic reticulum-stressed (ERS) head and neck squamous cell carcinoma (HNSCC) cells on macrophages. Methods This study was reviewed and approved by the Ethics Committee. The expression levels of ERS-associated proteins, including protein kinase R-like endoplasmic reticulum kinase (PERK) and glucose-regulated protein 78 (GRP78), in HNSCC tissues and para-tumor tissues were detected by Western blot (WB) and quantitative real-time PCR (RT-qPCR). HN4 human laryngeal squamous cell carcinoma cells were treated with 500 U/mL interferon-γ (IFN-γ) for 48 h to induce ER stress, and exosomes secreted by ER-stressed HN4 cells were collected and identified. The types of miRNAs in exosomes were identified through bioinformatics analysis, and the target genes of miRNAs were predicted. Macrophages were transfected with miRNA, co cultured with collected exosomes, and the expression of PTEN in macrophages was knocked down. The downstream signaling pathway regulated by exosomal miRNAs was studied by WB and RT-qPCR. Results Compared with that in para-tumor tissues, the expression level of ER stress-associated proteins in HNSCC tissues was increased (P<0.05). RNA-seq analysis revealed that miR-26a-5p was highly upregulated in ER-stressed HN4 cell-derived exosomes (P<0.05). PTEN is the target gene for miR-26a-5p. miR-26a-5p increased the expression level of PD-L1 in macrophages and downregulated the expression of PTEN (P<0.05). Macrophages co cultured with ERS extracellular vesicles showed an increase in miR-26a-5p and PD-L1 expression, a decrease in PTEN expression, and an increase in p-AKT expression (P<0.05). Knock down the expression of PTEN in macrophages and increase the expression of PD-L1 (P<0.01). Conclusion ERS HNSCC cell-derived exosomal miR-26a-5p promotes the expression of PD-L1 in macrophages through the PTEN/AKT signaling pathway.https://www.kqjbfz.com/CN/10.12016/j.issn.2096-1456.2024.01.003head and neck squamous cell carcinomaendoplasmic reticulum stressexosomemir-26a-5pmacrophageprogrammed death receptor ligand 1phosphate and tension homology deleted on chromsome tenprotein kinase b |
| spellingShingle | JIAO Pengfei WANG Zeyu WU Heming YAO Siyue WANG Huilin YAO Enhui ZHANG Yuyao YUAN Yi ZHONG Yi Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway 口腔疾病防治 head and neck squamous cell carcinoma endoplasmic reticulum stress exosome mir-26a-5p macrophage programmed death receptor ligand 1 phosphate and tension homology deleted on chromsome ten protein kinase b |
| title | Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway |
| title_full | Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway |
| title_fullStr | Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway |
| title_full_unstemmed | Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway |
| title_short | Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway |
| title_sort | endoplasmic reticulum stressed hnscc cell derived exosomal mir 26a 5p promotes pd l1 expression in macrophage through pten akt signaling pathway |
| topic | head and neck squamous cell carcinoma endoplasmic reticulum stress exosome mir-26a-5p macrophage programmed death receptor ligand 1 phosphate and tension homology deleted on chromsome ten protein kinase b |
| url | https://www.kqjbfz.com/CN/10.12016/j.issn.2096-1456.2024.01.003 |
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