M2 Macrophage-derived Exosome miR-1246 Regulates the Growth and Invasion of Gastric Cancer Cells

Liang ZHANG; Baoquan WANG; Xifeng LEI; Xu WANG; Yang KE; Wei ZHANG

doi:10.12259/j.issn.2095-610X.S20230724

Volume 44 Issue 7

Jul. 2023

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Liang ZHANG, Baoquan WANG, Xifeng LEI, Xu WANG, Yang KE, Wei ZHANG. M2 Macrophage-derived Exosome miR-1246 Regulates the Growth and Invasion of Gastric Cancer Cells[J]. Journal of Kunming Medical University, 2023, 44(7): 69-77. doi: 10.12259/j.issn.2095-610X.S20230724

Citation:

Liang ZHANG, Baoquan WANG, Xifeng LEI, Xu WANG, Yang KE, Wei ZHANG. M2 Macrophage-derived Exosome miR-1246 Regulates the Growth and Invasion of Gastric Cancer Cells[J]. Journal of Kunming Medical University, 2023, 44(7): 69-77. doi: 10.12259/j.issn.2095-610X.S20230724

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M2 Macrophage-derived Exosome miR-1246 Regulates the Growth and Invasion of Gastric Cancer Cells

doi: 10.12259/j.issn.2095-610X.S20230724

Liang ZHANG¹,
Baoquan WANG¹,
Xifeng LEI¹,
Xu WANG¹,
Yang KE^{2
,
,},
Wei ZHANG^{1
,
,}

1.
Dept. of General Surgery，Weinan Central Hospital，Weinan Shanxi 714000
2.
Dept. of Hepatobiliary and Pancreatic Surgery，The 2nd Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101，China

Received Date: 2023-04-19
Available Online: 2023-07-17
Publish Date: 2023-07-25

Abstract

Abstract

Objective To investigate the effects of M2 macrophage-derived exosome miR-1246 on the proliferation, apoptosis and invasion of AGS cells. Methods After induction of M2 macrophages using LPS and IFN-γ, their exosomes were isolated and identified by transmission electron microscopy and western blot. After M2 macrophages were transfected with NC inhibitor and miR-1246 inhibitor respectively, the corresponding exosomes were isolated and co-cultured with AGS cells, and proliferation, apoptosis, and invasion of AGS cells were detected by CCK-8, Annexin V-FITC/PI and Transwell, respectively. TargetScan database predicted miR-1246 downstream targets and the targeting relationship between miR-1246 and GSK3B was validated by dual-luciferase reporter gene assays. Results The exosomes isolated from M2 macrophages were 30-150 nm in size and expressed ALIX, CD63 and TSG101. M2 macrophage-derived exosomes increased the viability and invasive cell count of AGS cells and decreased their apoptotic ratio. Phenotypic changes in AGS cells were reverted by knocking down the expression of miR-1246 in exosomes. Exosome miR-1246 targets GSK3B and upregulated the expression of β-catenin and c-Myc. Conclusion M2 macrophage-derived exosome miR-1246 mediates Wnt pathway activation to promote proliferation and invasion of gastric cancer cells and inhibit their apoptosis via targeting GSK3B.
- Gastric cancer,
- Macrophages,
- Exosomes,
- miR-1246,
- Wnt signaling pathway

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References(30)

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