Targeting the Radiation-Induced ARv7-Mediated circNHS/miR-512-5p/XRCC5 Signaling With Quercetin Signaling Increases Prostate Cancer Radiosensitivity

BackgroundRadiation therapy (RT) with androgen deprivation therapy (ADT) is an effective therapy to suppress the locally advanced prostate cancer (PCa). However, we unexpected found that RT could also inducing the androgen receptor splice variant 7 (ARv7) expression to decrease the radiosensitivity. MethodsThe study was designed to target ARv7 expression with Quercetin or ARv7-shRNA led to enhancing increase the radiation sensitivity to better suppress the PCa that involved the modulating the circNHS/miR-512-5p/XRCC5 signaling.ResultsMechanism studies revealed that RT-induced ARv7 may function via altering the circNHS/miR-512-5p/XRCC5 signaling to decrease the radiosensitivity. Results from preclinical studies using multiple in vitro cell lines and in vivo mouse models concluded that combining RT with small molecule of Quercetin to target full-length AR and ARv7 could lead to better efficacy to suppress PCa progression. ConclusionTogether, these results suggest that ARv7 may play key roles to alter the PCa radiosensitivity, and targeting this newly identified ARv7 mediated circNHS/miR-512-5p/XRCC5 signaling with Quercetin may help us to develop a novel RT to better suppress the progression of PCa.