Abstract
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.
Highlights
Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary tract and its incidence ranks fifth among malignant tumors worldwide and second among male malignancies
After androgen deprivation treatment (ADT) treatment with a median time of 18–24 months, almost all patients gradually evolved into castration-resistant prostate cancer (CRPC) [2], and 86% of CRPC eventually turned into metastatic castration-resistant prostate cancer [3]
It was shown that the Family With Sequence Similarity 64 Member A (FAM64A) mRNA level was significantly higher in prostate cancer (PCa) tissue compared with normal prostate tissue (Fig. 1a)
Summary
Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary tract and its incidence ranks fifth among malignant tumors worldwide and second among male malignancies. Due to PCa patients have no obvious symptoms in the early stage, the majority of them are diagnosed in the late stage, resulting in a low cure rate and higher mortality rate. For patients with advanced PCa, the current standard firstline treatment is androgen deprivation treatment (ADT), which can effectively reduce tumor burden, improve patient quality of life and prolong overall survival time. Activated AR molecules can both enhance and inhibit the expression of genes related to PCa progression. This hormone-driven AR signal is essential for the development, differentiation, and normal function of the prostate. CRPC continues to express AR and AR regulatory genes after androgen ablation therapy [4]
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