Exosome-derived miR-27a produced by PSC-27 cells contributes to prostate cancer chemoresistance through p53

Abstract Prostate cancer (PCa) is a major malignancy in men. Hitherto that date, surgical or chemical castration is the standard treatment to PCa. Nevertheless, there are still many patients with initial treatment progress to metastatic castration-resistant prostate cancer (mCRPC). There are many effective chemotherapeutic drugs for mCRPC, but the tumors will be resistant to these chemotherapeutic drugs, which is an urgent problem to be solved. Specifically, tumor therapy resistance driven by the pathologically active host stroma has gradually becoming the spotlight of oncotherapy in recent years. The exosome-derived miR-27a plays an important role in PCa cell chemoresistance. However, the functions of miR-27a on PCa developing chemoresistance remain unknown. In the present study, we aimed to construct potential regulatory networks of exosomal miR-27a in PCa chemoresistance. The expression of miR-27a was significantly increased by treatment with cisplatin, doxorubicin (DOX) and docetaxel in PCa tissues. We next co-cultured PCa cells (PC3 cells) with primary prostate fibroblasts (PSC27 cells) to explore the mechanisms of tumor therapy resistance. Further studies delineate that exosome-derived miR-27a produced by PSC-27 cells improved chemoresistance by restraining the expression of P53 gene. Our studies provide a new direction for exploring the effects of PCa tumor microenvironment of chemoresistance.