Abstract
The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states. The molecular regulation of COX-2 gene expression is normally tightly regulated on transcriptional and post-transcriptional levels. However, loss of function at either level of COX-2 gene regulation promotes constitutive COX-2 overexpression which plays a key role in carcinogenesis, particularly colorectal tumorigenesis. Current work investigating the regulatory mechanisms of COX-2 expression has demonstrated post-transcriptional regulation to play a central role. Rapid COX-2 mRNA decay and translational inhibition is mediated through a conserved AU-rich element (ARE) present within the 3-untranslated region (3UTR). The COX-2 ARE exerts its control through association with ARE RNA-binding proteins. These trans-acting regulatory factors influence the fate of COX-2 mRNA by controlling mRNA degradation, stabilization, or translation. Recent evidence demonstrates the functional significance rapid mRNA decay and translational inhibition play in controlling COX-2 gene expression and that, if dysregulated, allow for overexpression of COX-2 and other associated angiogenic factors detected in neoplasia.
Keywords: cox, cyclooxygenase, prostaglandins, cancer, post-transcriptional regulation, mrna stability, au-rich element, rna-binding protein
Current Pharmaceutical Design
Title: Dysregulated Post-Transcriptional Control of COX-2 Gene Expression in Cancer
Volume: 10 Issue: 6
Author(s): Dan A. Dixon
Affiliation:
Keywords: cox, cyclooxygenase, prostaglandins, cancer, post-transcriptional regulation, mrna stability, au-rich element, rna-binding protein
Abstract: The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states. The molecular regulation of COX-2 gene expression is normally tightly regulated on transcriptional and post-transcriptional levels. However, loss of function at either level of COX-2 gene regulation promotes constitutive COX-2 overexpression which plays a key role in carcinogenesis, particularly colorectal tumorigenesis. Current work investigating the regulatory mechanisms of COX-2 expression has demonstrated post-transcriptional regulation to play a central role. Rapid COX-2 mRNA decay and translational inhibition is mediated through a conserved AU-rich element (ARE) present within the 3-untranslated region (3UTR). The COX-2 ARE exerts its control through association with ARE RNA-binding proteins. These trans-acting regulatory factors influence the fate of COX-2 mRNA by controlling mRNA degradation, stabilization, or translation. Recent evidence demonstrates the functional significance rapid mRNA decay and translational inhibition play in controlling COX-2 gene expression and that, if dysregulated, allow for overexpression of COX-2 and other associated angiogenic factors detected in neoplasia.
Export Options
About this article
Cite this article as:
Dixon A. Dan, Dysregulated Post-Transcriptional Control of COX-2 Gene Expression in Cancer, Current Pharmaceutical Design 2004; 10 (6) . https://dx.doi.org/10.2174/1381612043453171
DOI https://dx.doi.org/10.2174/1381612043453171 |
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
-
Melanoma
Current Cancer Therapy Reviews Gene Transfer and Drug Delivery with Electric Pulse Generators
Current Drug Metabolism MicroRNA-31 Inhibits Lung Adenocarcinoma Stem-Like Cells via Down-Regulation of MET-PI3K-Akt Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry New Perspectives in the Treatment of Melanoma: Anti-Angiogenic and Anti-Lymphangiogenic Strategies
Recent Patents on Anti-Cancer Drug Discovery Understanding the Interaction Between Human Serum Albumin and Anti-Bacterial/ Anti-Cancer Compounds
Current Pharmaceutical Design Characterization of Pharmaceutical IgG and Biosimilars Using Miniaturized Platforms and LC-MS/MS
Current Pharmaceutical Biotechnology The Current State of Potential Therapeutic Modalities for Glioblastoma Multiforme: A Clinical Review
Current Drug Metabolism Potential Usage of ING Family Members in Cancer Diagnostics and Molecular Therapy
Current Drug Targets Recent Advances in Receptor-Targeted Fluorescent Probes for In Vivo Cancer Imaging
Current Medicinal Chemistry Recent Developments in the Field of Anticancer Platinum Complexes
Recent Patents on Anti-Cancer Drug Discovery The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment
Current Medicinal Chemistry Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway
Anti-Cancer Agents in Medicinal Chemistry The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy
Current Cancer Drug Targets Antibodies as Crypts of Antiinfective and Antitumor Peptides
Current Medicinal Chemistry Improving Cancer Therapeutics by Molecular Profiling
Current Drug Metabolism Patents Related to Cancer Stem Cell Research
Recent Patents on DNA & Gene Sequences Recent Advances of Metallocenes for Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry Isoform-Selective PI3K Inhibitors for Various Diseases
Current Topics in Medicinal Chemistry Cellular Signaling Crosstalk Between Multiple Receptors for Investigation of Pathophysiology in Multifactorial Diseases - What is Clinically-Relevant Crosstalk?
Current Medicinal Chemistry The Central Role of Angiotensin I-Converting Enzyme in Vertebrate Pathophysiology
Current Topics in Medicinal Chemistry