Abstract
HOXA10 plays an important role in the body structure and development. Recently, patterns of deregulated HOX expression have been identified in various cancers. Meanwhile, WT1 is closely associated with the HOXA10 gene, which is an inducible transcription factor . We hypothesized that during the process of the ovarian cancer pathogenesis, the HOXA10 promoter CpG hypomethylation coupled with decreased WT1 expression could co-regulate HOXA10 expression. After the treatment of 5-Aza-dC, ovarian cancer cell lines(SKOV-3 and HEY) significantly increased HOXA10 expression. Transfection of HOXA10 siRNA with SKOV-3 and HEY ovarian cancer cell lines significantly downregulated HOXA10 expression but upregulated WT1 expression, compared to the control siRNA transfection. In ovarian cancer samples, the HOXA10 expression is significantly high. Nevertheless, the expression of HOXA10 is low in normal ones(P<0.05). We tried to use the method of methylation-specific PCR(MSP) to find the CpG sites, which are located in the scope of the WT1’s core-binding consensus(GCGG). In ovarian cancer samples, methylation prevalence was extremely high with the low expression of HOXA10. However, in the normal ovarian samples, the methylation prevalence was lower with the high expression of HOXA10(P<0. 05). In all samples of epithelial and normal ovarian samples collected, the WT1 expression with the promoter CpG hypomethylation of HOXA10 both contribute to the regulation of HOXA10 expression. That is to say, HOXA10 promoter methylationpositive combined with the WT1-positive result in the low expression of HOXA10. On the other hand, the HOXA10 expression was the highest in methylation-negative and WT1-negative samples.
Keywords: HOXA10, WT1, hypomethylation, ovarian cancer, siRNA, 5-Aza-dC, Bisulfite DNA sequencing and Methylation-specific PCR.
Current Pharmaceutical Design
Title:Transcription Factor WT1 and Promoter CpG Hypomethylation Coactivate HOXA10 Expression in Ovarian Cancer
Volume: 20 Issue: 11
Author(s): Yi Jiang, Yongli Chu, Weiwei Tang, Yicong Wan, Lin Zhang and Wenjun Cheng
Affiliation:
Keywords: HOXA10, WT1, hypomethylation, ovarian cancer, siRNA, 5-Aza-dC, Bisulfite DNA sequencing and Methylation-specific PCR.
Abstract: HOXA10 plays an important role in the body structure and development. Recently, patterns of deregulated HOX expression have been identified in various cancers. Meanwhile, WT1 is closely associated with the HOXA10 gene, which is an inducible transcription factor . We hypothesized that during the process of the ovarian cancer pathogenesis, the HOXA10 promoter CpG hypomethylation coupled with decreased WT1 expression could co-regulate HOXA10 expression. After the treatment of 5-Aza-dC, ovarian cancer cell lines(SKOV-3 and HEY) significantly increased HOXA10 expression. Transfection of HOXA10 siRNA with SKOV-3 and HEY ovarian cancer cell lines significantly downregulated HOXA10 expression but upregulated WT1 expression, compared to the control siRNA transfection. In ovarian cancer samples, the HOXA10 expression is significantly high. Nevertheless, the expression of HOXA10 is low in normal ones(P<0.05). We tried to use the method of methylation-specific PCR(MSP) to find the CpG sites, which are located in the scope of the WT1’s core-binding consensus(GCGG). In ovarian cancer samples, methylation prevalence was extremely high with the low expression of HOXA10. However, in the normal ovarian samples, the methylation prevalence was lower with the high expression of HOXA10(P<0. 05). In all samples of epithelial and normal ovarian samples collected, the WT1 expression with the promoter CpG hypomethylation of HOXA10 both contribute to the regulation of HOXA10 expression. That is to say, HOXA10 promoter methylationpositive combined with the WT1-positive result in the low expression of HOXA10. On the other hand, the HOXA10 expression was the highest in methylation-negative and WT1-negative samples.
Export Options
About this article
Cite this article as:
Jiang Yi, Chu Yongli, Tang Weiwei, Wan Yicong, Zhang Lin and Cheng Wenjun, Transcription Factor WT1 and Promoter CpG Hypomethylation Coactivate HOXA10 Expression in Ovarian Cancer, Current Pharmaceutical Design 2014; 20 (11) . https://dx.doi.org/10.2174/13816128113199990545
DOI https://dx.doi.org/10.2174/13816128113199990545 |
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
-
Multifunctional Materials for Cancer Therapy: From Antitumoral Agents to Innovative Administration
Current Organic Chemistry Purification of Cinnamic Acid and Aporphine Alkaloids from Enicosanthellum pulchrum Twig Extract and their Biological Activities
The Natural Products Journal Bispecific Antibodies: An Innovative Arsenal to Hunt, Grab and Destroy Cancer Cells
Current Pharmaceutical Biotechnology Patent Annotations
Recent Patents on Anti-Cancer Drug Discovery Non-Viral Delivery of RNA Interference Targeting Cancer Cells in Cancer Gene Therapy
Current Gene Therapy 2-(2-Arylidenehydrazinyl) Thiazol-4(5H)-ones as Epidermal Growth Factor Receptor Inhibitors: A Combined Quantitative Structure Activity Relationship and Pharmacophore Study
Current Enzyme Inhibition Vascular Endothelial Growth Factor (VEGF) Biochemistry and Development of Inhibitory Drugs
Current Drug Therapy Oncogenic Role of SET/I2PP2A for Gynecologic Cancers
Current Drug Targets Verbascoside Attenuates Rac-1 and HIF-1α Signaling Cascade in Colorectal Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Curcumin Conjugates and Metallocomplexes as Lead Compounds for Development of Anticancer Agents - A Short Review
Current Bioactive Compounds Amplified Crosstalk Between Estrogen Binding and GFR Signaling Mediated Pathways of ER Activation Drives Responses in Tumors Treated with Endocrine Disruptors
Recent Patents on Anti-Cancer Drug Discovery Chemokine Like Receptor-1 (CMKLR-1) Receptor: A Potential Therapeutic Target in Management of Chemerin Induced Type 2 Diabetes Mellitus and Cancer
Current Pharmaceutical Design The Akt Pathway: Molecular Targets for Anti-Cancer Drug Development
Current Cancer Drug Targets Patent Selections
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Gene Therapy for Bone Regeneration
Current Pharmaceutical Design Modulation of Aquaporins by Dietary Patterns and Plant Bioactive Compounds
Current Medicinal Chemistry Thermodynamic and Kinetic Aspects Involved in the Development of Nanocarriers and Drug Delivery Systems Based on Cationic Biopolymers
Current Pharmaceutical Design Targeting Clusterin Induces Apoptosis, Reduces Growth Ability and Invasion and Mediates Sensitivity to Chemotherapy in Human Osteosarcoma Cells
Current Pharmaceutical Biotechnology Engineering Nanomedicines to Overcome Multidrug Resistance in Cancer Therapy
Current Medicinal Chemistry Evaluation and Management of Adnexal Masses in Postmenopausal Women
Current Women`s Health Reviews