Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis

• Published in: Current pharmaceutical design Vol. 27; no. 41; p. 4261
• Main Authors: Liu, Bo, Jiang, Hui-Yang, Yuan, Tao, Zhou, Wei-Dong, Xiang, Zhen-Dong, Jiang, Qi-Quan, Wu, Deng-Long
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2021
• Subjects: Androgen Antagonists; Cell Line, Tumor; Cell Proliferation - genetics; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Oncogenes; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; ADT; ceRNA; miR-15b; AFAP1-AS1; Prostate cancer; IGF1R
• ISSN: 1873-4286
• DOI: 10.2174/1381612827666210612052317

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. 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). 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. 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.