Gastric cancer cell-derived exosomal miR-541-5p induces M2 macrophage polarization through DUSP3/JAK2/STAT3 pathway.
BMC Cancer
; 24(1): 957, 2024 Aug 06.
Article
in En
| MEDLINE
| ID: mdl-39103776
ABSTRACT
PURPOSE:
Exosomal microRNAs have been identified as important mediators of communication between tumor cells and macrophages in the microenvironment. miR-541-5p was reported to be involved in hepatocellular carcinoma progression, but its role in gastric cancer (GC) and in GC cell-macrophage crosstalk is unknown.METHODS:
Cell proliferation, migration and invasion were respectively assessed by CCK-8 assay, scratch and Transwell assays. RT-qPCR was used to detect the level of miR-541-5p, macrophage markers and DUSP3. The percentage of CD11b+CD206+ cell population was analyzed by flow cytometry. Western blotting was employed to evaluate DUSP3-JAK2/STAT3 pathway proteins and exosome markers. The interaction between miR-541-5p and DUSP3 was verified by luciferase assay.RESULTS:
The results showed that miR-541-5p was upregulated in GC tissues and cells, and stimulated GC cell growth, migration and invasion in vitro. GC cells induce M2 macrophage polarization by secreting the exosomal miR-541-5p. Exosomal miR-541-5p maintained JAK2/STAT3 pathway activation in macrophages by targeting negative regulation of DUSP3. Inhibiting miR-541-5p significantly limited tumor growth in vivo.CONCLUSION:
In conclusion, miR-541-5p promotes GC cell progression. GC cells may induce macrophage M2 polarization through the exosomal miR-541-5p-mediated DUSP3/JAK2/STAT3 pathway. miR-541-5p may be a potential therapeutic target for GC.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
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MicroRNAs
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Cell Proliferation
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STAT3 Transcription Factor
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Janus Kinase 2
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Dual Specificity Phosphatase 3
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Exosomes
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Macrophages
Limits:
Animals
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Female
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Humans
/
Male
Language:
En
Journal:
BMC Cancer
Year:
2024
Document type:
Article