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Updated: Jul 16, 2025
Author Spotlight: Exploring the Mechanisms of MicroRNA Loading into Extracellular Vesicles in Cancer Progression
Published on: October 6, 2023
M2 Macrophage-Derived Extracellular Vesicles Containing MicroRNA-501-3p Promote Colon Cancer Progression Through the
Yuanyi Ding1, Huijin Zhao2, Wenbo Niu1
1The Second Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
Background:
Macrophage-derived extracellular vesicles with microRNAs can cause and develop colon cancer.
Objective:
To investigate M2 macrophage-derived extracellular vesicles and colon cancer.
Design:
A prospective and experimental study of M2 macrophage-derived extracellular vesicles in colon cancer.
Setting:
This study was completed at the Fourth Hospital of Hebei Medical University.
Patients:
Patients with colon cancer who had undergone surgical resection.
Main Outcome Measures:
Suppressor of cytokine signaling 3, miR-501-3p, SET domain containing 7, and DNA methyltransferase 1 were measured in colon cancer samples. Multiple experiments determined suppressor of cytokine signaling 3, miR-501-3p, SET domain containing 7, and DNA methyltransferase 1 binding affinity. M2 macrophages were cultivated from M0 macrophages isolated from peripheral blood mononuclear cells of a healthy donor and polarized to produce extracellular vesicles. Gain- or loss-of-function tests using colon cancer cells and M2 macrophage-derived extracellular vesicles revealed cell biological processes. Finally, animal models were created to test how miR-501-3p from M2-extracellular vesicles affects tumor growth via the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3.
Results:
Colon cancer increased miR-501-3p and DNA methyltransferase 1 and downregulated suppressor of cytokine signaling 3 and SET domain containing 7. miR-151-3p inhibited SET domain containing 7, upregulating DNA methyltransferase 1. Increased promoter methylation by DNA methyltransferase 1 decreased suppressor of cytokine signaling 3 expression. M2-EVs with miR-501-3p regulated the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to induce apoptosis and colon cancer cell growth, invasion, and migration. M2-EV-delivered miR-501-3p also regulated the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to promote tumor growth in animals.
Limitations:
Further research is needed in clinical application of M2 macrophage-derived extracellular vesicles containing miR-501-3p as a biomarker of colon cancer.
Conclusions:
M2 macrophage-derived extracellular vesicles with miR-501-3p regulate the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to promote colon cancer.
Las Vesculas Extracelulares Derivadas De Macrfagos M Que Contienen Microarnp Promueven La Progresin Del Cncer De Colon A Travs Del Eje Setd/Dnmt/Socs:
ANTECEDENTES:Las vesículas extracelulares derivadas de macrófagos con microARN pueden causar y desarrollar cáncer de colon.OBJETIVO:Investigamos las vesículas extracelulares derivadas de macrófagos M2 y el cáncer de colon.DISEÑO:Un estudio prospectivo y experimental de vesículas extracelulares derivadas de macrófagos M2 en el cáncer de colon.ESCENARIO:Este estudio se completó en el Cuarto Hospital de la Universidad Médica de Hebei.PACIENTES:Pacientes con cáncer de colon sometidos a resección quirúrgica.PRINCIPALES MEDIDAS DE RESULTADO:Se midieron el supresor de la señalización de citoquinas 3, miR-501-3p, SETD7 y la ADN metiltransferasa 1 en muestras de cáncer de colon. Múltiples experimentos determinaron la afinidad de unión del supresor de la señalización de citoquinas 3, de miR-501-3p, de SETD7 y de la ADN metiltransferasa 1. Los macrófagos M2 se cultivaron a partir de macrófagos M0 aislados de células mononucleares de sangre periférica de donantes sanos y se polarizaron para producir vesículas extracelulares. Las pruebas de ganancia o pérdida de función utilizando células de cáncer de colon y vesículas extracelulares derivadas de macrófagos M2 revelaron procesos biológicos celulares. Finalmente, se crearon modelos animales para probar cómo miR-501-3p de vesículas extracelulares M2 afecta el crecimiento tumoral a través del SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3.RESULTADOS:El cáncer de colon aumentó el miR-501-3p y la ADN metiltransferasa 1 y reguló negativamente el supresor de la señalización de citoquinas 3 y SETD7. miR-151-3p inhibió SETD7, regulando positivamente la ADN metiltransferasa 1. El aumento de la metilación del promotor por la ADN metiltransferasa 1 produjo disminución de la expresión del supresor de señalización de citocinas 3. Los M2-EV con miR-501-3p regularon el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para inducir apoptosis y crecimiento, invasión y migración de células de cáncer de colon. El miR-501-3p administrado por M2-EV también reguló el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para promover el crecimiento tumoral en animales.LIMITACIONES:Se necesita más investigación en la aplicación clínica de vesículas extracelulares derivadas de macrófagos M2 que contienen miR-501-3p como biomarcador de cáncer de colon.CONCLUSIONES:Las vesículas extracelulares derivadas de macrófagos M2 con miR-501-3p regulan el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para promover el cáncer de colon. (Traducción-Dr. Felipe Bellolio ).
Insights
Macrophage-derived extracellular vesicles carrying miR-501-3p promote colon cancer progression. These vesicles regulate the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis, impacting tumor growth and cell behavior.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Macrophage-derived extracellular vesicles (MVs) containing microRNAs are implicated in colon cancer development.
- M2 macrophages, a subtype of macrophages, play a role in tumor progression and are a focus of this study.
Purpose of the Study:
- To investigate the role of M2 macrophage-derived extracellular vesicles (MVs) in colon cancer.
- To elucidate the molecular mechanisms by which M2 MVs influence colon cancer cell behavior and tumor growth.
Main Methods:
- Prospective and experimental study design involving M2 MVs and colon cancer cells.
- Analysis of key molecules (SOCS3, miR-501-3p, SETD7, DNMT1) in colon cancer samples and their binding affinities.
- In vitro gain/loss-of-function studies using colon cancer cells and M2 MVs, and in vivo animal models.
Main Results:
- Colon cancer tissues showed altered expression of miR-501-3p, DNMT1, SOCS3, and SETD7.
- M2 MVs carrying miR-501-3p were found to regulate the SETD7/DNMT1/SOCS3 axis.
- This regulation promoted colon cancer cell growth, invasion, migration, and apoptosis, and enhanced tumor growth in animal models.
Conclusions:
- M2 macrophage-derived extracellular vesicles containing miR-501-3p promote colon cancer.
- The miR-501-3p within M2 MVs exerts its effects by regulating the SETD7/DNMT1/SOCS3 signaling pathway.
- Further research into M2 MV-derived miR-501-3p as a potential colon cancer biomarker is warranted.
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