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BMSC derived EVs inhibit colorectal Cancer progression by transporting MAGI2-AS3 or something similar.
- Source :
-
Cellular signalling [Cell Signal] 2024 Sep; Vol. 121, pp. 111235. Date of Electronic Publication: 2024 May 26. - Publication Year :
- 2024
-
Abstract
- In this study, we investigated the molecular mechanisms underlying the impact of extracellular vesicles (EVs) derived from bone marrow stromal cells (BMSCs) on colorectal cancer (CRC) development. The focus was on the role of MAGI2-AS3, delivered by BMSC-EVs, in regulating USP6NL DNA methylation-mediated MYC protein translation modification to promote CDK2 downregulation. Utilizing bioinformatics analysis, we identified significant enrichment of MAGI2-AS3 related to copper-induced cell death in CRC. In vitro experiments demonstrated the downregulation of MAGI2-AS3 in CRC cells, and BMSC-EVs were found to deliver MAGI2-AS3 to inhibit CRC cell proliferation, migration, and invasion. Further exploration revealed that MAGI2-AS3 suppressed MYC protein translation modification by regulating USP6NL DNA methylation, leading to CDK2 downregulation and prevention of colorectal cancer. Overexpression of MYC reversed the functional effects of BMSC-EVs-MAGI2-AS3. In vivo experiments validated the inhibitory impact of BMSC-EVs-MAGI2-AS3 on CRC tumorigenicity by promoting CDK2 downregulation through USP6NL DNA methylation-mediated MYC protein translation modification. Overall, BMSC-EVs-MAGI2-AS3 may serve as a potential intervention to prevent CRC occurrence by modulating key molecular pathways.<br />Competing Interests: Declaration of competing interest The author declares no conflict of interest.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Cell Proliferation
Adaptor Proteins, Signal Transducing metabolism
Mesenchymal Stem Cells metabolism
Cell Line, Tumor
Cell Movement
Mice, Nude
DNA Methylation
Disease Progression
Gene Expression Regulation, Neoplastic
Cyclin-Dependent Kinase 2 metabolism
Proto-Oncogene Proteins c-myc metabolism
Mice, Inbred BALB C
Guanylate Kinases
Colorectal Neoplasms pathology
Colorectal Neoplasms metabolism
Extracellular Vesicles metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3913
- Volume :
- 121
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 38806109
- Full Text :
- https://doi.org/10.1016/j.cellsig.2024.111235