MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer
Abstract The tumor microenvironment (TME) plays an important role in tumorigenesis and development. Tumor-associated macrophages (TAMs) are essential members of the TME, the exosomes and miRNAs they secrete are crucial in tumor regulation. Our previous study showed that GRP78-induced macrophages inf...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07466-7 |
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| author | Jinmiao Tian Lichao Zhang Xiaoqin La Xiaxia Fan Zhuoyu Li |
| author_facet | Jinmiao Tian Lichao Zhang Xiaoqin La Xiaxia Fan Zhuoyu Li |
| author_sort | Jinmiao Tian |
| collection | DOAJ |
| description | Abstract The tumor microenvironment (TME) plays an important role in tumorigenesis and development. Tumor-associated macrophages (TAMs) are essential members of the TME, the exosomes and miRNAs they secrete are crucial in tumor regulation. Our previous study showed that GRP78-induced macrophages infinitely tend to be M2-type TAMs. In this study, the exosomes of M0 and GRP78-induced macrophage were collected and co-incubated with colorectal cancer (CRC) cells. The results implied that macrophage exosomes induced by GRP78 (GRP78-exos) significantly promoted stemness and chemoresistance in CRC in vitro and in vivo. Further, the top 5 miRNAs upregulated in GRP78-exos were obtained from miRNA sequencing data. The qRT-PCR validation revealed that miR-769-5p was the most observably upregulated and could be directly transferred into CRC cells via GRP78-exos. Mechanistically, the study indicated that miR-769-5p targeted MAPK1 to regulate the cell cycle-related proteins RB1, cyclin D1, and cyclin E1. This contributes to CRC cells entering a quiescent state, which leads to the development of chemoresistance. Moreover, miR-769-5p is also expressed higher in the tissues of 5-FU-resistant CRC patients. In summary, the findings indicate a novel function of miR-769-5p as a potential marker for the diagnosis and treatment of chemotherapy resistance in CRC. |
| format | Article |
| id | doaj-art-458d5153939c47dc94b1f3bc3e0dcf0e |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-458d5153939c47dc94b1f3bc3e0dcf0e2025-08-20T02:59:57ZengNature Publishing GroupCell Death and Disease2041-48892025-03-0116111410.1038/s41419-025-07466-7MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancerJinmiao Tian0Lichao Zhang1Xiaoqin La2Xiaxia Fan3Zhuoyu Li4Key Laboratory of Chemical Biology and Molecular Engineering of the National Ministry of Education, Institute of Biotechnology, Shanxi UniversityInstitutes of Biomedical Sciences, Shanxi UniversityInstitutes of Biomedical Sciences, Shanxi UniversityKey Laboratory of Chemical Biology and Molecular Engineering of the National Ministry of Education, Institute of Biotechnology, Shanxi UniversityKey Laboratory of Chemical Biology and Molecular Engineering of the National Ministry of Education, Institute of Biotechnology, Shanxi UniversityAbstract The tumor microenvironment (TME) plays an important role in tumorigenesis and development. Tumor-associated macrophages (TAMs) are essential members of the TME, the exosomes and miRNAs they secrete are crucial in tumor regulation. Our previous study showed that GRP78-induced macrophages infinitely tend to be M2-type TAMs. In this study, the exosomes of M0 and GRP78-induced macrophage were collected and co-incubated with colorectal cancer (CRC) cells. The results implied that macrophage exosomes induced by GRP78 (GRP78-exos) significantly promoted stemness and chemoresistance in CRC in vitro and in vivo. Further, the top 5 miRNAs upregulated in GRP78-exos were obtained from miRNA sequencing data. The qRT-PCR validation revealed that miR-769-5p was the most observably upregulated and could be directly transferred into CRC cells via GRP78-exos. Mechanistically, the study indicated that miR-769-5p targeted MAPK1 to regulate the cell cycle-related proteins RB1, cyclin D1, and cyclin E1. This contributes to CRC cells entering a quiescent state, which leads to the development of chemoresistance. Moreover, miR-769-5p is also expressed higher in the tissues of 5-FU-resistant CRC patients. In summary, the findings indicate a novel function of miR-769-5p as a potential marker for the diagnosis and treatment of chemotherapy resistance in CRC.https://doi.org/10.1038/s41419-025-07466-7 |
| spellingShingle | Jinmiao Tian Lichao Zhang Xiaoqin La Xiaxia Fan Zhuoyu Li MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer Cell Death and Disease |
| title | MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer |
| title_full | MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer |
| title_fullStr | MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer |
| title_full_unstemmed | MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer |
| title_short | MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer |
| title_sort | mir 769 5p of macrophage exosomes induced by grp78 promotes stemness and chemoresistance in colorectal cancer |
| url | https://doi.org/10.1038/s41419-025-07466-7 |
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