Tumor-associated macrophages of the M2 phenotype promote cancer initiation and progression. Importantly, M2 macrophage-derived exosomes play key roles in the malignancy of cancer cells. Here, we report that circTMCO3 is upregulated in ovarian cancer patients, and its high expression indicates poor survival. M2-derived exosomes promote proliferation, migration, and invasion in ovarian cancer, but these effects are abolished by knockdown of circTMCO3. Furthermore, circTMCO3 functions as a competing endogenous RNA for miR-515-5p to reduce its abundance, thus upregulating ITGA8 in ovarian cancer. miR-515-5p inhibits ovarian cancer malignancy via directly downregulating ITGA8. The decreased oncogenic activity of circTMCO3-silencing exosomes is reversed by miR-515-5p knockdown or ITGA8 overexpression. Exosomal circTMCO3 promotes ovarian cancer progression in nude mice. Thus, M2 macrophage-derived exosomes promote malignancy by delivering circTMCO3 and targeting the miR-515-5p/ITGA8 axis in ovarian cancer. Our findings not only provide mechanistic insights into ovarian cancer progression, but also suggest potential therapeutic targets.
Exosomes , Mice, Nude , MicroRNAs , Ovarian Neoplasms , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Humans , Exosomes/metabolism , Exosomes/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Mice , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Macrophages/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Cell Proliferation , Integrin alpha Chains/genetics , Integrin alpha Chains/metabolism , Cell Movement
