Circular RNA hsa_circ_0001610 promotes prostate cancer progression by sponging miR-1324 and upregulating PTK6.

ABSTRACT

Prostate cancer (PCa) incidence and cancer-related deaths are both high in the male population. Once castration-resistant prostate cancer (CRPC) has developed, PCa can be difficult to manage. Circular RNAs (circRNAs) play essential roles in the regulation of carcinogenesis and cancer progression. In CRPC, however, the potential molecular mechanisms and biological functions of circRNAs are yet to be defined. In this study, we conducted RNA sequencing on four hormone-sensitive prostate cancer (HSPC) tumor tissue samples and three CRPC samples. We recognized hsa_circ_0001610, a novel circRNA that was highly expressed in the cells and tissue of CRPC. We used quantitative real-time PCR (qRT-PCR) to evaluate hsa_circ_0001610 expression. We conducted in vivo and in vitro experiments and found that hsa_circ_0001610 overexpression caused PCa cells to proliferate and migrate and caused enzalutamide resistance. In contrast, the opposite results were found for hsa_circ_0001610 knockdown. We used Western blot, dual-luciferase reporter assays, RNA immunoprecipitation (RIP), qRT-PCR, and rescue experiments to reveal the underlying mechanisms of hsa_circ_0001610. Mechanistically, hsa_circ_0001610 acted as a molecular sponge for miR-1324 and thus reversed its inhibitory effect on its target gene PTK6. As a result, the PTK6 expression was enhanced, which accelerated PCa progression. The findings of this study confirmed that hsa_circ_0001610 drives the progression of PCa through the hsa_circ_0001610/miR-1324/PTK6 axis. Thus, hsa_circ_0001610 is potentially an effective therapeutic target and specific biomarker for advanced PCa.