Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200030, China.
Lab for Noncoding RNA and Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China.
Gene. 2024 Dec 20;930:148818. doi: 10.1016/j.gene.2024.148818. Epub 2024 Aug 2.
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.
前列腺癌（PCa）在男性人群中的发病率和癌症相关死亡率都很高。一旦发生去势抵抗性前列腺癌（CRPC），PCa 就难以治疗。环状 RNA（circRNA）在致癌和癌症进展的调控中发挥着重要作用。然而，在 CRPC 中，circRNA 的潜在分子机制和生物学功能尚未确定。在这项研究中，我们对四个激素敏感型前列腺癌（HSPC）肿瘤组织样本和三个 CRPC 样本进行了 RNA 测序。我们发现了一个在 CRPC 细胞和组织中高度表达的新型 circRNA，hsa_circ_0001610。我们使用定量实时 PCR（qRT-PCR）评估 hsa_circ_0001610 的表达。我们进行了体内和体外实验，发现 hsa_circ_0001610 的过表达导致 PCa 细胞增殖和迁移，并导致恩杂鲁胺耐药。相反，hsa_circ_0001610 敲低则产生相反的结果。我们使用 Western blot、双荧光素酶报告基因检测、RNA 免疫沉淀（RIP）、qRT-PCR 和挽救实验来揭示 hsa_circ_0001610 的潜在机制。从机制上讲，hsa_circ_0001610 作为 miR-1324 的分子海绵，从而逆转了其对靶基因 PTK6 的抑制作用。结果，PTK6 的表达增强，加速了 PCa 的进展。这项研究的结果证实，hsa_circ_0001610 通过 hsa_circ_0001610/miR-1324/PTK6 轴驱动 PCa 的进展。因此，hsa_circ_0001610 可能是晚期 PCa 的有效治疗靶点和特异性生物标志物。
