Gastric Cancer Cell-derived Exosomal MiR-541-5p Induces M2 Macrophage Polarization Through DUSP3/JAK2/STAT3 Pathway

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2024 Aug 5

PMID 39103776

Authors

Haimin Xiao

Jia Fu

Ruiting Liu

Likun Yan

Zheqi Zhou

Jinyan Yuan

Affiliations

Soon will be listed here.

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 CD11bCD206 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.

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