Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that have been recognized to regulate the expression of uncountable number of genes. Their aberrant expression has been found to be linked to the pathology of many diseases including cancer. There is a drive to develop miRNA targeted therapeutics for different diseases especially cancer. Nevertheless, reining in these short non-coding RNAs is not as straightforward as originally thought. This is in view of the recent discoveries that miRNAs are under epigenetic regulations at multiple levels. Exportin 5 protein (XPO5) nuclear export mediated regulation of miRNAs is one such important epigenetic mechanism. XPO5 is responsible for exporting precursor miRNAs through the nuclear membrane to the cytoplasm, and is thus a critical step in miRNA biogenesis. A number of studies have shown that variations in components of the miRNA biogenesis pathways, particularly the aberrant expression of XPO5, increase the risk of developing cancer. In addition to XPO5, the Exportin 1 protein (XPO1) or chromosome region maintenance 1 (CRM1) can also carry miRNA export function. These findings are supported by pathway analyses that reveal certain miRNAs as direct interaction partners of CRM1. An in depth understanding of miRNA export mediated regulatory mechanisms is important for the successful design of clinically viable therapeutics. In this review, we describe the current knowledge on the mechanisms of miRNA nuclear transport mediated regulation and propose strategies to selectively block this important mechanism in cancer.
Keywords: XPO5, XPO1, CRM1, nuclear export, small molecule inhibitors, selective inhibitors of nuclear export.
Current Drug Targets
Title:Nuclear Export Mediated Regulation of MicroRNAs: Potential Target for Drug Intervention
Volume: 14 Issue: 10
Author(s): Irfana Muqbil, Bin Bao, Abdul Badi Abou-Samra, Ramzi M. Mohammad and Asfar S. Azmi
Affiliation:
Keywords: XPO5, XPO1, CRM1, nuclear export, small molecule inhibitors, selective inhibitors of nuclear export.
Abstract: MicroRNAs (miRNAs) are short non-coding RNAs that have been recognized to regulate the expression of uncountable number of genes. Their aberrant expression has been found to be linked to the pathology of many diseases including cancer. There is a drive to develop miRNA targeted therapeutics for different diseases especially cancer. Nevertheless, reining in these short non-coding RNAs is not as straightforward as originally thought. This is in view of the recent discoveries that miRNAs are under epigenetic regulations at multiple levels. Exportin 5 protein (XPO5) nuclear export mediated regulation of miRNAs is one such important epigenetic mechanism. XPO5 is responsible for exporting precursor miRNAs through the nuclear membrane to the cytoplasm, and is thus a critical step in miRNA biogenesis. A number of studies have shown that variations in components of the miRNA biogenesis pathways, particularly the aberrant expression of XPO5, increase the risk of developing cancer. In addition to XPO5, the Exportin 1 protein (XPO1) or chromosome region maintenance 1 (CRM1) can also carry miRNA export function. These findings are supported by pathway analyses that reveal certain miRNAs as direct interaction partners of CRM1. An in depth understanding of miRNA export mediated regulatory mechanisms is important for the successful design of clinically viable therapeutics. In this review, we describe the current knowledge on the mechanisms of miRNA nuclear transport mediated regulation and propose strategies to selectively block this important mechanism in cancer.
Export Options
About this article
Cite this article as:
Muqbil Irfana, Bao Bin, Abou-Samra Badi Abdul, Mohammad M. Ramzi and Azmi S. Asfar, Nuclear Export Mediated Regulation of MicroRNAs: Potential Target for Drug Intervention, Current Drug Targets 2013; 14 (10) . https://dx.doi.org/10.2174/1389450111314100002
DOI https://dx.doi.org/10.2174/1389450111314100002 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...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
Related Articles
-
The Role of DNA Repair Pathways in AML Chemosensitivity
Current Drug Targets ROS1 Kinase Inhibitors for Molecular-Targeted Therapies
Current Medicinal Chemistry Immunomodulation Via Targeted Inhibition of Antigen Receptor Signal Transduction
Cardiovascular & Hematological Disorders-Drug Targets Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells
Current Medicinal Chemistry Structural and Functional Role of Gly281 in L-asparaginase from Erwinia carotovora
Protein & Peptide Letters Thalidomide Derived Immunomodulatory Drugs (IMiDs) as Potential Therapeutic Agents
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Recent Patents Reveal Microtubules as Persistent Promising Target for Novel Drug Development for Cancers
Recent Patents on Anti-Infective Drug Discovery Biotechnological Approaches for the Treatment of Inflammatory Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Recombinant Immunotoxins for the Treatment of Chemoresistant Hematologic Malignancies
Current Pharmaceutical Design Monoclonal Antibody Therapy in Haematological Malignancies
Current Clinical Pharmacology Anti-Angiogenic and Anti-Inflammatory Effects of Statins: Relevance to Anti-Cancer Therapy
Current Cancer Drug Targets Immune Checkpoint Inhibitors for Non-small-cell Lung Cancer: Does that Represent a ‘New Frontier’?
Anti-Cancer Agents in Medicinal Chemistry PI3K/AKT/mTOR Inhibitors In Ovarian Cancer
Current Medicinal Chemistry Targeting Bcl-2 in CLL
Current Medicinal Chemistry Whole Cell Biocatalysts for the Preparation of Nucleosides and their Derivatives
Current Pharmaceutical Design A Virtual Screening Approach for the Identification of High Affinity Small Molecules Targeting BCR-ABL1 Inhibitors for the Treatment of Chronic Myeloid Leukemia
Current Topics in Medicinal Chemistry Signaling in Human B-Lymphoma Rafts
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Significance of Transferrin Receptors in Oncology: the Development of Functional Nano-based Drug Delivery Systems
Current Drug Delivery Development of Anti-CD20 Antigen-Targeting Therapies for B-cell Lymphoproliferative Malignancies - The State of the Art
Current Drug Targets Embryonic Stem Cell MicroRNAs: Defining Factors in Induced Pluripotent (iPS) and Cancer (CSC) Stem Cells?
Current Stem Cell Research & Therapy