TAM-derived exosomal miR-589-3p accelerates ovarian cancer progression through BCL2L13

Abstract 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.