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Published on: August 2, 2024
TAM-derived exosomal miR-589-3p accelerates ovarian cancer progression through BCL2L13
Jianqing Wang1, Yan Zhu1, Yang He1
1Department of Gynecology and Obstetrics, Yancheng First People's Hospital, Yancheng Clinical College of Xuzhou Medical University, Yancheng, Jiangsu, 224002, China.
Background:
Tumor-associated macrophages (TAM) are critical elements of intercellular communication in tumor microenvironment (TME), and exosomes are key mediators between tumor cells and the TME. According to previous reports, miRNAs exert a pivotal role in ovarian cancer (OC) development. The purpose of this work was to explore the function of TAM-derived exosomal miR-589-3p in OC development and elucidate the underlying molecular mechanisms.
Methods:
First, peripheral blood mononuclear cells (PBMC) were treated with IL-4 and IL-13 to polarize them into M2-type macrophages. Exosomes were separated from M2-type macrophages, and the physical properties of exosomes were evaluated using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Next, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was applied to examine the expression of relevant genes. Subsequently, Targetscan and miRDB were utilized to predict miR-589-3p target genes, and then the interaction between miR-589-3p and BCL2L13 was verified by dual luciferase assay and RNA Binding Protein Immunoprecipitation (RIP) assay. Finally, Cell Counting Kit-8 (CCK-8) and flow cytometry experiments were employed to explore the changes in the proliferative and apoptotic abilities of OC cells.
Results:
In this research, we demonstrated that TAM-derived exosomes facilitated OC cell proliferation and suppressed OC cell apoptosis. Then, qRT-PCR results indicated that miR-589-3p were markedly elevated after co-culture of TAM-derived exosomes with OC cells. In addition, we discovered that miR-589-3p was bound to BCL-2-like protein 13 (BCL2L13), which was confirmed through luciferase assay and RIP assay. Furthermore, functional analysis displayed that TAM-derived exosomes treated with miR-589-3p inhibitor attenuated the promotion of OC cell progression by exosomes.
Conclusion:
TAM-derived exosomal miR-589-3p enhanced OC progression through BCL2L13, which offers a novel for OC therapy.
Insights
Tumor-associated macrophages (TAM) release exosomes containing miR-589-3p, which promote ovarian cancer (OC) progression by targeting BCL2L13. Inhibiting this exosomal microRNA offers a potential therapeutic strategy for OC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Tumor-associated macrophages (TAM) are key in the tumor microenvironment (TME).
- Exosomes mediate intercellular communication between tumor cells and the TME.
- MicroRNAs (miRNAs) play a crucial role in ovarian cancer (OC) development.
Purpose of the Study:
- To investigate the role of TAM-derived exosomal miR-589-3p in OC progression.
- To elucidate the molecular mechanisms underlying miR-589-3p's function in OC.
Main Methods:
- Polarization of peripheral blood mononuclear cells (PBMCs) into M2-type macrophages.
- Isolation and characterization of exosomes using TEM and NTA.
- qRT-PCR to quantify gene expression.
- Bioinformatic prediction and experimental validation (dual luciferase, RIP assays) of miR-589-3p targets.
- Assessment of OC cell proliferation and apoptosis using CCK-8 and flow cytometry.
Main Results:
- TAM-derived exosomes promote OC cell proliferation and inhibit apoptosis.
- miR-589-3p expression is upregulated in OC cells co-cultured with TAM-derived exosomes.
- miR-589-3p directly targets and binds to BCL2L13.
- Inhibiting miR-589-3p in TAM-derived exosomes attenuates OC progression.
Conclusions:
- TAM-derived exosomal miR-589-3p promotes OC progression by targeting BCL2L13.
- This finding presents a novel therapeutic target for ovarian cancer.
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