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
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...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
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
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
The Origin and Identification of Mesenchymal Stem Cells in Teeth: from Odontogenic to Non-odontogenic
Current Stem Cell Research & Therapy Current Methods and Research Progress in Nanomaterials Risk Assessment
Current Drug Metabolism Biology of Circulating Nucleic Acids and Possible Roles in Diagnosis and Treatment in Diabetes and Cancer
Infectious Disorders - Drug Targets Understanding Autophagy in Cell Death Control
Current Pharmaceutical Design Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Unravelling the Antioxidant Potential, Alpha-Glucosidase Inhibitory Activity and Phenolic Composition of Dendrocalamus strictus Plantations Generated Biomass Waste (Leaves)
The Natural Products Journal Preliminary Experience with Yttrium-90-labelled Rituximab (Chimeric Anti CD-20 Antibody) in Patients with Relapsed and Refractory B Cell Non-Hodgkins Lymphoma
Current Radiopharmaceuticals Fertility Preservation for Young Women with Cancer: Hope for the Future
Current Women`s Health Reviews Targeting the Mitochondrial Electron Transport Chain Complexes for the Induction of Apoptosis and Cancer Treatment
Current Pharmaceutical Biotechnology Encountering and Advancing Through Antiangiogenesis Therapy for Gliomas
Current Pharmaceutical Design Applications of Solid-State Fermentation Process in Biological Detoxification of Industrial Wastes
Current Biochemical Engineering (Discontinued) Phenolic Contents and Antioxidant Activity of Helicteres Hirsuta Extracts
Letters in Organic Chemistry Diagnostic Imaging of Fetal and Neonatal Abdominal and Soft Tissue Tumors
Current Pediatric Reviews HSV-1 Viral Oncolysis and Molecular Imaging with PET
Current Cancer Drug Targets Oridonin, a Promising Antitumor Natural Product in the Chemotherapy of Hematological Malignancies
Current Pharmaceutical Biotechnology Mining the Adenovirus "Virome" for Systemic Oncolytics
Current Pharmaceutical Biotechnology Anti-breast Cancer Potential of Natural and Synthetic Coumarin Derivatives
Current Topics in Medicinal Chemistry Antitumoral Potential of Snake Venom Phospholipases A2 and Synthetic Peptides
Current Pharmaceutical Biotechnology Human Cancer Cell Line Based Approach of 1,3,4-thiadiazole and its Fused Ring: A Comprehensive Review
Anti-Cancer Agents in Medicinal Chemistry Protein Kinase C ζ Drives Sphingomyelin Metabolism in the Nucleus During Cell Proliferation
Current Chemical Biology