Exosomal transfer of tumor-associated macrophage-derived hsa_circ_0001610 reduces radiosensitivity in endometrial cancer.

The occurrence of radioresistance is a clinical obstacle to endometrial cancer (EC) treatment and induces tumor relapse. In this study, we found that tumor-associated macrophages (TAMs) enriched in EC specimens were determined to present an M2-like phenotype. In vitro, the coculture of M2-polarized macrophages significantly downregulated the radiosensitivity of EC cells by releasing exosomes. Hsa_circ_0001610 was found to be abundant in exosomes derived from M2-polarized macrophages (EXOs), and hsa_circ_0001610 knockdown eliminated the reduction effect of EXOs on the radiosensitivity of EC cells. The following mechanism research revealed that hsa_circ_0001610 functioned as the competing endogenous RNA of miR-139-5p, thereby upregulating cyclin B1 expression, which is a vital pusher of radioresistance in several types of cancer by regulating the cell cycle. Hsa_circ_0001610 overexpression reduced the radiosensitivity of EC cells, which was then reversed by miR-139-5p overexpression. In vivo, the promotion effect of EXOs on xenograft tumor growth in nude mice treated with irradiation was further reinforced after hsa_circ_0001610 overexpression. In conclusion, TAM-derived exosomes transferred hsa_circ_0001610 to EC cells, and the overexpressed hsa_circ_0001610 in EC cells released cyclin B1 expression through adsorbing miR-139-5p, thereby weakening the radiosensitivity of EC cells.