Abstract
DNA methyltransferase 1 (DNMT1) plays a significant role in maintaining DNA methylation. Aberrant DNA methylation is a recognized feature of human cancers and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports also have suggested that folate deficiency was associated with many cancers. The aim of the present study was to evaluate the effect of folate deficiency and aberrant expression of DNA methyltransferase 1 (DNMT1) on cervical cancerization. The expression of DNMT1 protein and mRNA and levels of serum folate were detected in 238 women with a diagnosis of normal cervix (NC,n = 53), cervical intraepithelial neoplasia (CIN I, n = 52; CIN II/III, n = 53), and squamous cell carcinoma of the cervix (SCC; n = 80). In addition, the expression of DNMT1 protein and mRNA was measured in cervical cancer cells (Caski and C33A) treated by different concentration of folate. Serum folate levels decreased and expression levels of DNMT1 protein and mRNA increased gradually with progressive severity of the cervix lesions (P<0.001). It was found that folate was able to reduce the viability of Caski or C33A cell (r=0.978, P=0.002; r=0.984, P<0.001) and regulated aberrant expression of DNMT1 protein (r=-0.859, P=0.01; r=-0.914, P<0.001) and mRNA (r=-0.297, P=0.159; r=0.433, P=0.034) in vitro. Our findings indicated that the low-level of serum folate and high-expression of DNMT1 protein or mRNA was significantly associated with cervical carcinogenesis. Folate deficiency and aberrant expression of DNA methyltransferase 1 had additive effect on cervical cancerization. Folate supplement and recovery of aberrant DNA methylation status may offer a new strategy for prevention and therapy of cancers.
Keywords: Folate, DNA methyltransferase 1 (DNMT1), Cervical cancerization, Cervical cancer cells.
Current Pharmaceutical Design
Title:Folate Deficiency and Aberrant Expression of DNA Methyltransferase 1 were Associated with Cervical Cancerization
Volume: 20 Issue: 11
Author(s): Wang Jin-tao, Ding Ling, Jiang Shi-Wen, Hao Junxia, Zhao Wei-min, Zhou Qin, Yang Zuo-kai and Zhang Li
Affiliation:
Keywords: Folate, DNA methyltransferase 1 (DNMT1), Cervical cancerization, Cervical cancer cells.
Abstract: DNA methyltransferase 1 (DNMT1) plays a significant role in maintaining DNA methylation. Aberrant DNA methylation is a recognized feature of human cancers and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports also have suggested that folate deficiency was associated with many cancers. The aim of the present study was to evaluate the effect of folate deficiency and aberrant expression of DNA methyltransferase 1 (DNMT1) on cervical cancerization. The expression of DNMT1 protein and mRNA and levels of serum folate were detected in 238 women with a diagnosis of normal cervix (NC,n = 53), cervical intraepithelial neoplasia (CIN I, n = 52; CIN II/III, n = 53), and squamous cell carcinoma of the cervix (SCC; n = 80). In addition, the expression of DNMT1 protein and mRNA was measured in cervical cancer cells (Caski and C33A) treated by different concentration of folate. Serum folate levels decreased and expression levels of DNMT1 protein and mRNA increased gradually with progressive severity of the cervix lesions (P<0.001). It was found that folate was able to reduce the viability of Caski or C33A cell (r=0.978, P=0.002; r=0.984, P<0.001) and regulated aberrant expression of DNMT1 protein (r=-0.859, P=0.01; r=-0.914, P<0.001) and mRNA (r=-0.297, P=0.159; r=0.433, P=0.034) in vitro. Our findings indicated that the low-level of serum folate and high-expression of DNMT1 protein or mRNA was significantly associated with cervical carcinogenesis. Folate deficiency and aberrant expression of DNA methyltransferase 1 had additive effect on cervical cancerization. Folate supplement and recovery of aberrant DNA methylation status may offer a new strategy for prevention and therapy of cancers.
Export Options
About this article
Cite this article as:
Jin-tao Wang, Ling Ding, Shi-Wen Jiang, Junxia Hao, Wei-min Zhao, Qin Zhou, Zuo-kai Yang and Li Zhang, Folate Deficiency and Aberrant Expression of DNA Methyltransferase 1 were Associated with Cervical Cancerization, Current Pharmaceutical Design 2014; 20 (11) . https://dx.doi.org/10.2174/13816128113199990543
DOI https://dx.doi.org/10.2174/13816128113199990543 |
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
-
Vehicles for Lipophilic Drugs: Implications for Experimental Design, Neuroprotection, and Drug Discovery
Current Neurovascular Research Patent Selections
Recent Patents on Biotechnology Current Status and Future Perspectives of Chemoprevention in Head and Neck Cancer
Current Cancer Drug Targets An Update on Overcoming MDR1-Mediated Multidrug Resistance in Cancer Chemotherapy
Current Pharmaceutical Design Multifunctional Materials for Cancer Therapy: From Antitumoral Agents to Innovative Administration
Current Organic Chemistry Review of Chemoradiotherapy for High-Risk Prostate Cancer
Reviews on Recent Clinical Trials Aloperine Induces Apoptosis by a Reactive Oxygen Species Activation Mechanism in Human Ovarian Cancer Cells
Protein & Peptide Letters The New Patient and Responsible Self-Medication Practices: A Critical Review
Current Drug Safety Streamlined In Vivo Selection and Screening of Human Prostate Carcinoma Avid Phage Particles for Development of Peptide Based In Vivo Tumor Imaging Agents
Combinatorial Chemistry & High Throughput Screening The Effect of Educational Intervention Based on Health Belief Model on Beliefs Towards Human Papillomavirus Vaccination in a Sample of Iranian Female Nursing Students
Current Women`s Health Reviews Functions of Antimicrobial Peptides in Vertebrates
Current Protein & Peptide Science Neurocysticercosis: The Enigmatic Disease
Central Nervous System Agents in Medicinal Chemistry Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Anticancer Peptides and Proteins: A Panoramic View
Protein & Peptide Letters Synthesis, Immunomodulation and Cytotoxic Effects of Vanadium (IV) Complexes
Medicinal Chemistry Head and Neck Cancer Treatments through Chemotherapy to Magnetic Systems: Perspectives and Challenges
Current Radiopharmaceuticals Translational Research of Optical Molecular Imaging for Personalized Medicine
Current Molecular Medicine Inflammation and Anemia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Putative Mechanisms of Viral Transmission and Molecular Dysregulation of Mammary Epithelial Cells by Human Papillomavirus: Implications for Breast Cancer
Current Molecular Medicine Expression of Specificity Protein Transcription Factors in Pancreatic Cancer and their Association in Prognosis and Therapy
Current Medicinal Chemistry