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

Ma, Tianyi; Wang, Meng; Wang, Song; Hu, Hanqing; Zhang, Xin; Wang, Hufei; Wang, Guiyu; Jin, Yinghu

Ma, Tianyi; Wang, Meng; Wang, Song; Hu, Hanqing; Zhang, Xin; Wang, Hufei; Wang, Guiyu; Jin, Yinghu.

Afiliación

Ma T; Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
Wang M; Department of Colorectal Surgery, Zhejiang Cancer Hospital (Affiliated Cancer Hospital of the Chinese Academy of Sciences), Hangzhou 310000, China.
Wang S; Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
Hu H; Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
Zhang X; Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
Wang H; Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
Wang G; Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China. Electronic address: guiywang@163.com.
Jin Y; Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China. Electronic address: 33887443@qq.com.

Cell Signal ; 121: 111235, 2024 Sep.

Article en En | MEDLINE | ID: mdl-38806109

ABSTRACT

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.

Asunto(s)

Neoplasias Colorrectales; Vesículas Extracelulares; Humanos; Neoplasias Colorrectales/patología; Neoplasias Colorrectales/metabolismo; Vesículas Extracelulares/metabolismo; Animales; Ratones; Proliferación Celular; Proteínas Adaptadoras Transductoras de Señales/metabolismo; Células Madre Mesenquimatosas/metabolismo; Línea Celular Tumoral; Movimiento Celular; Ratones Desnudos; Metilación de ADN; Progresión de la Enfermedad; Regulación Neoplásica de la Expresión Génica; Quinasa 2 Dependiente de la Ciclina/metabolismo; Proteínas Proto-Oncogénicas c-myc/metabolismo; Ratones Endogámicos BALB C; Guanilato-Quinasas

Palabras clave

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

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Vesículas Extracelulares Límite: Animals / Humans Idioma: En Revista: Cell Signal Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

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