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.
Keywords: Prostate cancer, ADT, AFAP1-AS1, ceRNA, miR-15b, IGF1R.
Current Pharmaceutical Design
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.
Export Options
About this article
Cite this article as:
Liu Bo , Jiang Hui-Yang , Yuan Tao, Zhou Wei-Dong , Xiang Zhen-Dong, Jiang Qi-Quan and Wu Deng-Long*, Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis, Current Pharmaceutical Design 2021; 27 (41) . https://dx.doi.org/10.2174/1381612827666210612052317
DOI https://dx.doi.org/10.2174/1381612827666210612052317 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Inflammation and Cancer: When NF-κB Amalgamates the Perilous Partnership
Current Cancer Drug Targets Targeting Mitochondrial Biogenesis to Treat Insulin Resistance
Current Pharmaceutical Design The Association of Very High Hair Manganese Accumulation and High Oxidative Stress in Mongolian People
Current Aging Science Nanomedical Applications of Amphiphilic Dendrimeric Micelles
Current Medicinal Chemistry Computational Investigation of Ligand Binding of Flavonoids in Cytochrome P450 Receptors
Current Pharmaceutical Design The Effect of Alcohol on Gastrointestinal Motility
Reviews on Recent Clinical Trials The Role of Mammalian Target of Rapamycin (mTOR) Inhibitors in the Treatment of Solid Tumors
Current Cancer Therapy Reviews Recent Patents of Gene Sequences Relative to the Phosphatidylinositol 3-kinase / Akt Pathway and their Relevance to Drug Discovery
Recent Patents on DNA & Gene Sequences Two Diseases with One Hit: Inhibiting a Potential Diabetes Target to Reduce Cancer Risk and to Improve Anti-Cancer Therapy
Current Cancer Therapy Reviews A Review on Development and Characterization of a Cost-effective Targeted Quality-driven Antimalarial Product with an Emphasis on Phytosomes
Current Drug Targets Monofunctional Platinum (PtII) Compounds – Shifting the Paradigm in Designing New Pt-based Anticancer Agents
Current Medicinal Chemistry Potentiating Effect of Ethnomedicinal Plants Against Proliferation on Different Cancer Cell Lines
Current Drug Metabolism Nanomaterials for Photohyperthermia: A Review
Current Pharmaceutical Design Current Management of In Situ and Invasive Cervical Adenocarcinoma
Current Women`s Health Reviews Roles of miRNA in the Initiation and Development of Colorectal Carcinoma
Current Pharmaceutical Design Cyclophilin A as a Target of Cisplatin Chemosensitizers
Current Cancer Drug Targets A Facile Synthesis and Anticancer Activity Evaluation of Spiro Analogues of Benzothiazolylchromeno/pyrano Derivatives
Letters in Drug Design & Discovery Increased Neuronal Injury in Clock Gene Per-1 Deficient-Mice after Cerebral Ischemia
Current Neurovascular Research Natural and Semi synthetic Antimalarial Compounds: Emphasis on the Terpene Class
Mini-Reviews in Medicinal Chemistry The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy?
Current Drug Targets