MiR-200b is upregulated in plasma-derived exosomes and functions as an oncogene by promoting macrophage M2 polarization in ovarian cancer

BACKGROUND: Ovarian cancer is the seventh most common cancer in women and the second most reason of gynecologic cancer-related death. Growing evidence showed that exosomal miRNA plays a crucial role in the progression of ovarian cancer. METHODS: Exosomes were identified using nanoparticle tracking analysis, transmission electron microscopy and marker proteins detection. The levels of mRNA and proteins were ensured by qRT-PCR and western blot, respectively. Immunofluorescence, flow cytometry and ELISA assay were carried out to analyze macrophages polarization. CCK-8 and Transwell assay were used to measure the cell viability and invasion of ovarian cancer cells. The interaction of miR-200b and Kruppel like factor 6 (KLF6) was ensured by using luciferase reporter assay. RESULTS: Here, we obtained plasma-derived exosomes successfully, and proved that miR-200b was increased in the exosomes of ovarian cancer patients. Subsequently, our data showed that increasing of miR-200b could promote macrophage M2 polarization, but inhibit M1 polarization. miR-200b-overexpressed macrophages-conditioned medium notably enhanced the cell viability and invasion of ovarian cancer cells. Moreover, increasing of miR-200b inhibited KLF6 expression, while decreasing of miR-200b promoted KLF6 expression. Overexpression of KLF6 recused miR-200b-induced macrophage polarization toward M2, and the inhibitory effect of miR-200b on M1 polarization. CONCLUSIONS: Overall, our results demonstrated that miR-200b was highly expressed in the plasma-derived exosome of ovarian cancer patients, and promoted the proliferation and invasion of ovarian cancer cells through inducing macrophage M2 polarization by suppressing KLF6 expression. Our results suggested that miR-200b might be a novel target for ovarian cancer treatment.