Abstract
Hepatocellular carcinoma (HCC) is one of the few cancers with a worldwide increasing trend of incidence, representing the third largest cause of cancer-related death. The initiation and progression of HCC depend on progressive accumulation of genetic and epigenetic defects that alter an array of signaling cascades via deregulation of signal activators and inhibitors. MicroRNAs (miRNAs) are small RNA molecules that post-transcriptionally repress gene expression including those signal molecules and thus are critical for many cellular pathways. However, the balance of this fine-tuning function is broken by the abnormal expression of miRNAs in various cancers through genomic alterations or epigenetic mechanisms. This review summarizes the current knowledge of the role of epigenetic aberrations, including histone methylation and deacetylation as well as DNA hypermethylation and hypomethylation in the aberrant regulation of miRNAs leading to activation of signaling pathways such as Ras, STAT3 and AKT/mTOR in HCC. Conceivably, the therapeutic efficacy of current chromatin-modifying drugs might be related to their capacity to reactivate previously silenced tumor-suppressive miRNAs and cause down-regulation of target oncogenes. Better understanding of the epigenetics-miRNA regulatory cascades in the control of the functionally significant pathways will provide new opportunities for the development of more effective therapeutic modality for HCC.
Keywords: Histone modifications, DNA hypermethylation and hypomethylation, hepatocellular carcinoma, signal transduction pathways, epigenetic defects, signal activators, MicroRNAs (miRNAs), gene expression, STAT3, AKT/mTOR
Current Pharmaceutical Design
Title:Epigenetic Deregulation of MicroRNAs: New Opportunities to Target Oncogenic Signaling Pathways in Hepatocellular Carcinoma
Volume: 19 Issue: 7
Author(s): Zhuo Yu and Alfred Sze-Lok Cheng
Affiliation:
Keywords: Histone modifications, DNA hypermethylation and hypomethylation, hepatocellular carcinoma, signal transduction pathways, epigenetic defects, signal activators, MicroRNAs (miRNAs), gene expression, STAT3, AKT/mTOR
Abstract: Hepatocellular carcinoma (HCC) is one of the few cancers with a worldwide increasing trend of incidence, representing the third largest cause of cancer-related death. The initiation and progression of HCC depend on progressive accumulation of genetic and epigenetic defects that alter an array of signaling cascades via deregulation of signal activators and inhibitors. MicroRNAs (miRNAs) are small RNA molecules that post-transcriptionally repress gene expression including those signal molecules and thus are critical for many cellular pathways. However, the balance of this fine-tuning function is broken by the abnormal expression of miRNAs in various cancers through genomic alterations or epigenetic mechanisms. This review summarizes the current knowledge of the role of epigenetic aberrations, including histone methylation and deacetylation as well as DNA hypermethylation and hypomethylation in the aberrant regulation of miRNAs leading to activation of signaling pathways such as Ras, STAT3 and AKT/mTOR in HCC. Conceivably, the therapeutic efficacy of current chromatin-modifying drugs might be related to their capacity to reactivate previously silenced tumor-suppressive miRNAs and cause down-regulation of target oncogenes. Better understanding of the epigenetics-miRNA regulatory cascades in the control of the functionally significant pathways will provide new opportunities for the development of more effective therapeutic modality for HCC.
Export Options
About this article
Cite this article as:
Yu Zhuo and Sze-Lok Cheng Alfred, Epigenetic Deregulation of MicroRNAs: New Opportunities to Target Oncogenic Signaling Pathways in Hepatocellular Carcinoma, Current Pharmaceutical Design 2013; 19 (7) . https://dx.doi.org/10.2174/138161213804805757
DOI https://dx.doi.org/10.2174/138161213804805757 |
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
-
Novel Molecular Targets and Mechanisms Involved in the Invasion and Metastasis of Pancreatic Cancer
Clinical Cancer Drugs Anticancer Perspectives on the Fungal-Derived Polyphenolic Hispolon
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Potential of Perineural Invasion, Hypoxia and Desmoplasia in Pancreatic Cancer
Current Pharmaceutical Design Bladder Cancer and Stem Cells
Current Signal Transduction Therapy Drug Metabolism and Drug Interactions: Application and Clinical Value of In Vitro Models
Current Drug Metabolism Human Sirtuins: An Overview of an Emerging Drug Target in Age-Related Diseases and Cancer
Current Drug Targets Radiolabelled Oligonucleotides for Imaging of Gene Expression with PET
Current Medicinal Chemistry Angiogenesis Inhibitors: Current & Future Directions
Current Pharmaceutical Design Molecular and Thermodynamic Studies on DNA Triplex Formed in the Promoter Region of HMGB1 Gene as a Selective Target for Anticancer Drugs
Anti-Cancer Agents in Medicinal Chemistry Targeting NS5B RNA-Dependent RNA Polymerase for Anti-HCV Chemotherapy
Current Drug Targets - Infectious Disorders Mast Cells as Target in Cancer Therapy
Current Pharmaceutical Design Targeting Histone Deacetylases for the Treatment of Immune, Endocrine & Metabolic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets Orthotopic Liver Transplantation in Non-Alcoholic Fatty Liver Disease Patients
Reviews on Recent Clinical Trials Rationale for Designing of Antigen-Specific Immune Therapy Including Dendritic Cell-Based Therapy in Patients with Chronic Hepatitis B Virus Infection
Anti-Infective Agents in Medicinal Chemistry Receptor Tryosine Kinase Inhibitors as Potent Weapons in War Against Cancers
Current Pharmaceutical Design Recent Advances in the Development of Novel Therapeutics Targeting Dendritic Cells
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Targeting the Cancer-Stroma Interaction: A Potential Approach for Pancreatic Cancer Treatment
Current Pharmaceutical Design Paclitaxel Formulations: Challenges and Novel Delivery Options
Current Drug Delivery The Role of Radiopharmaceuticals in Amiodarone-Induced Thyroid Pathology
Current Radiopharmaceuticals Novel Concepts for Anti-Infective Activity of Cytokines, Chemokines and Diverse Agents
Recent Patents on Anti-Infective Drug Discovery