Title:Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis
Volume: 27
Issue: 41
Author(s): Bo Liu, Hui-Yang Jiang, Tao Yuan, Wei-Dong Zhou, Zhen-Dong Xiang, Qi-Quan Jiang and Deng-Long Wu*
Affiliation:
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo, Shanghai 200065,China
Keywords:
Prostate cancer, ADT, AFAP1-AS1, ceRNA, miR-15b, IGF1R.
Abstract:
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.
