LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling

Previous studies suggest that cadmium (Cd) is one of the causative factors of prostate cancer (PCa), but the effect of chronic Cd exposure on PCa progression remains unclear. Besides, whether long noncoding RNAs (lncRNAs) are involved in the regulation of prolonged exposure to Cd in PCa needs to be elucidated. In the present study, we found that the serum concentration of Cd in PCa patients was positively correlated with the Gleason score and tumor-node-metastasis (TNM) classification. To simulate chronic Cd exposure in PCa, we subjected PC3 and DU145 cells to long-term, low-dose Cd exposure and further examined tumor behavior. Functional studies identified that chronic Cd exposure promoted cell growth and ferroptosis resistance in vitro and in vivo. Furthermore, we found that lncRNA OIP5-AS1 expression was greatly elevated in PC3 and DU145 cells upon chronic Cd exposure. Dysregulation of OIP5-AS1 expression mediated cell growth and Cd-induced ferroptosis. Mechanistically, we demonstrated that OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, our data indicate that lncRNA OIP5-AS1 promotes PCa progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling.