2. Academic Validation
  3. BMSC derived EVs inhibit colorectal Cancer progression by transporting MAGI2-AS3 or something similar

BMSC derived EVs inhibit colorectal Cancer progression by transporting MAGI2-AS3 or something similar

  • Cell Signal. 2024 Sep:121:111235. doi: 10.1016/j.cellsig.2024.111235.
Tianyi Ma 1,  Meng Wang 2,  Song Wang 3,  Hanqing Hu 1,  Xin Zhang 1,  Hufei Wang 1,  Guiyu Wang 4,  Yinghu Jin 5
Affiliations

Affiliations

  • 1 Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
  • 2 Department of Colorectal Surgery, Zhejiang Cancer Hospital (Affiliated Cancer Hospital of the Chinese Academy of Sciences), Hangzhou 310000, China.
  • 3 Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
  • 4 Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China. Electronic address: [email protected].
  • 5 Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China. Electronic address: [email protected].
PMID: 38806109 DOI: 10.1016/j.cellsig.2024.111235
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.

Keywords

CDK2 downregulation; Colorectal cancer; Extracellular vesicles; MAGI2-AS3; MYC protein translation modification; USP6NL DNA methylation.

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