Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
Department of Surgery, Fuwai Hospital Chinese Academic of Medical Science Shenzhen, University of South China, Shenzhen, China.
Cell Death Dis. 2021 Jul 2;12(7):668. doi: 10.1038/s41419-021-03933-z.
Endocrine therapy for prostate cancer (PCa) mainly inhibits androgen receptor (AR) signaling, due to increased androgen synthesis and AR changes, PCa evolved into castration-resistant prostate cancer (CRPC). The function of Family With Sequence Similarity 64 Member A (FAM64A) and its association with prostate cancer has not been reported. In our research, we first reported that FAM64A is up-regulated and positively associated with poor prognosis of patients with prostate cancer (PCa) by TCGA database and immunohistochemistry staining. Moreover, knockdown of FAM64A significantly suppressed the proliferation, migration, invasion, and cell cycle of PCa cells in vitro. Mechanistically, FAM64A expression was increased by dihydrotestosterone (DHT) through direct binding of AR to FAM64A promoter, and notably promoted the proliferation, migration, invasion, and cell cycle of androgen-dependent cell line of PCa. In addition, abnormal expression of FAM64A affects the immune and interferon signaling pathway of PCa cells. In conclusion, FAM64A was up-regulated by AR through directly binding to its specific promoter region to promote the development of PCa, and was associated with the immune mechanism and interferon signaling pathway, which provided a better understanding and a new potential for treating PCa.
用于前列腺癌 (PCa) 的内分泌疗法主要抑制雄激素受体 (AR) 信号，由于雄激素合成和 AR 变化增加，PCa 演变为去势抵抗性前列腺癌 (CRPC)。Family With Sequence Similarity 64 Member A (FAM64A) 的功能及其与前列腺癌的关联尚未报道。在我们的研究中，我们首先通过 TCGA 数据库和免疫组织化学染色报告 FAM64A 上调，并与前列腺癌 (PCa) 患者的预后不良呈正相关。此外，FAM64A 的敲低显著抑制了体外 PCa 细胞的增殖、迁移、侵袭和细胞周期。在机制上，DHT 通过 AR 与 FAM64A 启动子的直接结合增加 FAM64A 的表达，并显著促进雄激素依赖性 PCa 细胞系的增殖、迁移、侵袭和细胞周期。此外，FAM64A 的异常表达会影响 PCa 细胞的免疫和干扰素信号通路。总之，AR 通过直接结合其特定的启动子区域上调 FAM64A 以促进 PCa 的发展，并与免疫机制和干扰素信号通路相关，这为更好地理解和治疗 PCa 提供了新的潜在靶点。
