AHR suppresses cisplatin-induced apoptosis in ovarian cancer cells by regulating XIAP

Abstract

X-linked inhibitor of apoptosis protein (XIAP) plays a crucial role in cisplatin-induced apoptosis in ovarian cancer, whereas the molecular mechanism of how its expression is dysregulated remains unclear. Here, we report that the aryl hydrocarbon receptor (AHR) acts as a competitive endogenous RNA (ceRNA) of XIAP and can regulate its expression. Overexpression of AHR 3′UTR decreased, while AHR knockdown increased, the cisplatin-induced apoptotic rate in ovarian cancer cells. We also found that one microRNA (miRNA), miR-142-5p, can bind to both AHR and XIAP 3′UTRs and regulate their expression levels. Furthermore, AHR 3′UTR and miR-142-5p can occupy the same Ago2 to form an RNA-induced silencing complex (RISC). In addition, we showed that the effect of AHR overexpression on cisplatin-induced apoptosis could be rescued by either XIAP siRNA or miR-142-5p mimic. Thus, our findings reveal important insights into the molecular mechanism underlying the dysregulation of XIAP in ovarian cancer, indicating that AHR serves as the ceRNA that competes miR-142-5p with XIAP and subsequently affects the platinum-based chemotherapy.