Intronic Circular RNA hsa_circ_0092339 Plays as Molecular Sponge in Castration-resistance Prostate Cancer by hsa-mir-940/C-MYC Axis

Generally, only exonic circular RNA is believed to play the role as molecular sponge, while the main function of intronic circular RNA is regulating the expression of its parental gene. We aimed to find out whether intronic circular RNA could also act as molecular sponge in castration-resistance prostate cancer. Gene chip of castration-resistant and hormone-sensitive prostate cancer cell lines was sequenced to identify the differentially expressed circular RNA. We demonstrated that intronic circular RNA hsa_circ_0092339, located in the nucleus, was highly expressed in castration-resistance prostate cancer (CRPC) cell lines by using high throughput RNA sequencing. By knocking down hsa_circ_0092339, we found that this intronic circular RNA did not regulate the expression of its parental gene. By RIP and RNA pull-down experiment, we further found hsa_circ_0092339 realized its function by acting as molecular sponge. Hsa_circ_0092339 prevented degradation of C-MYC by absorbing hsa-mir-940 and preventing it enter the cytoplasm from nucleus. The combination of hsa-mir-940 and C-MYC was certified by dual-luciferase assay. In addition, we proved this axis was also effective in CRPC xenografted model. The effectiveness of this pathway in tissues was verified by animal experiments. Overall design: RNA-sequencing after hsa_circ_0092339 was knocking down in LNCaP-AI cell line