دورية أكاديمية
Musashi-2 potentiates colorectal cancer immune infiltration by regulating the post-translational modifications of HMGB1 to promote DCs maturation and migration
| العنوان: | Musashi-2 potentiates colorectal cancer immune infiltration by regulating the post-translational modifications of HMGB1 to promote DCs maturation and migration |
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| المؤلفون: | Xiaole Meng, Risi Na, Xiao Peng, Hui Li, Wanxin Ouyang, Wenting Zhou, Xuting You, Yuhuan Li, Xin Pu, Ke Zhang, Junjie Xia, Jie Wang, Huamei Tang, Guohong Zhuang, Zhihai Peng |
| المصدر: | Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-24 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Cytology |
| مصطلحات موضوعية: | Musashi-2, HMGB1, Post-translational modifications (PTMs), Immune infiltration, Colorectal cancer (CRC), Medicine, Cytology, QH573-671 |
| الوصف: | Abstract Post-translational modifications (PTMs) of the non-histone protein high-mobility group protein B1 (HMGB1) are involved in modulating inflammation and immune responses. Recent studies have implicated that the RNA-binding protein (RBP) Musashi-2 (MSI2) regulates multiple critical biological metabolic and immunoregulatory functions. However, the precise role of MSI2 in regulating PTMs and tumor immunity in colorectal cancer (CRC) remains unclear. Here, we present data indicating that MSI2 potentiates CRC immunopathology in colitis-associated colon cancer (CAC) mouse models, cell lines and clinical specimens, specifically via HMGB1-mediated dendritic cell (DC) maturation and migration, further contributes to the infiltration of CD4+ and CD8+ T cells and inflammatory responses. Under stress conditions, MSI2 can exacerbate the production, nucleocytoplasmic transport and extracellular release of damage-associated molecular patterns (DAMPs)-HMGB1 in CRC cells. Mechanistically, MSI2 mainly enhances the disulfide HMGB1 production and protein translation via direct binding to nucleotides 1403–1409 in the HMGB1 3′ UTR, and interacts with the cytoplasmic acetyltransferase P300 to upregulate its expression, further promoting the acetylation of K29 residue in HMGB1, thus leading to K29-HMGB1 nucleocytoplasmic translocation and extracellular release. Furthermore, blocking HMGB1 activity with glycyrrhizic acid (Gly) attenuates MSI2-mediated immunopathology and immune infiltration in CRC in vitro and in vivo. Collectively, this study suggests that MSI2 may improve the prognosis of CRC patients by reprogramming the tumor immune microenvironment (TIME) through HMGB1-mediated PTMs, which might be a novel therapeutic option for CRC immunotherapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1478-811X |
| Relation: | https://doaj.org/toc/1478-811X |
| DOI: | 10.1186/s12964-024-01495-z |
| URL الوصول: | https://doaj.org/article/ea1da2c16f25456d9ab05c03cce9a716 |
| رقم الأكسشن: | edsdoj.1da2c16f25456d9ab05c03cce9a716 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1478811X |
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| DOI: | 10.1186/s12964-024-01495-z |