Bo Liu, Hui-Yang Jiang, Tao Yuan, Wei-Dong Zhou, Zhen-Dong Xiang, Qi-Quan Jiang and Deng-Long Wu* Pages 4261 - 4269 ( 9 )
Background: Prostate cancer (PCa) is a commonly diagnosed malignant cancer and is the second- highest cause of cancer death in men worldwide. Enzalutamide is the second-generation inhibitor of androgen receptor signaling and is the fundamental drug for the treatment of advanced PCa. However, the disease will eventually progress to metastatic castration-resistant prostate cancer (CRPC) and aggressive neuroendocrine prostate cancer (NEPC) because of androgen-deprivation therapy (ADT) resistance. The aim of the study was to investigate the role of long non-coding RNA (lncRNA) AFAP1-AS1 in ADT resistance.
Methods: Quantitative real-time PCR analysis (qPCR) was used to assess the expression of AFAP1-AS1 in PCa cell lines and tissues. Cell proliferation and invasion were assessed after AFAP1-AS1 knockdown using Cell Counting Kit (CCK)-8 and Transwell assay, respectively. A dual-luciferase reporter gene assay was carried out to validate the regulatory relationship among AFAP1-AS1, microRNA (miR)-15b, and insulin-like growth factor1 receptor (IGF1R).
Results: AFAP1-AS1 level was markedly increased in castration-resistant C4-2 cells and NE-like cells (PC3, DU145, and NCI-H660), compared with androgen-sensitive LNCaP cells. Enzalutamide treatment increased the expression of AFAP1-AS1 in vitro and in vivo. Functionally, AFAP1-AS1 knockdown repressed tumor cell proliferation and invasion. Mechanistically, AFAP1-AS1 functioned as an oncogene in PCa through binding to miR-15b and destroying its tumor suppressor function. Finally, we identified that AFAP1-AS1 up-regulated IGF1R expression by competitively binding to miR-15b to de-repress IGF1R.
Conclusion: AFAP1-AS1 facilitates PCa progression by regulating miR-15b/IGF1R axis, indicating that AFAP1-AS1 may serve as a diagnostic biomarker and therapeutic target for PCa.
Prostate cancer, ADT, AFAP1-AS1, ceRNA, miR-15b, IGF1R.
Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065, Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065, Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065, Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065, Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065, Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065, Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065