ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Re-expression of Selected Epigenetically Silenced Candidate Tumor Suppressor Genes in Cervical Cancer by TET2-directed Demethylation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- TET2: a critical regulatory hub with broad therapeutic implications across human diseases.Frontiers in immunology · 2026Review
- Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines.Epigenetics · 2025Article
- Dissecting the epigenetic regulation of the fetal hemoglobin genes to unravel a novel therapeutic approach for β-hemoglobinopathies.Nucleic acids research · 2025Article
- How chronic inflammation fuels carcinogenesis as an environmental epimutagen.Discover oncology · 2025Review
- Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications.Cell chemical biology · 2024Review
- The role of aberrant DNA methylation in cancer initiation and clinical impacts.Therapeutic advances in medical oncology · 2024Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- The Mechanism of DNA Methylation and miRNA in Breast Cancer.International journal of molecular sciences · 2023Review
- Targeted DNA Demethylation: Vectors, Effectors and Perspectives.Biomedicines · 2023Review
- Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma.Clinical epigenetics · 2023Article
- Review
- Enzyme-free targeted DNA demethylation using CRISPR-dCas9-based steric hindrance to identify DNA methylation marks causal to altered gene expression.Nature protocols · 2022Review
- Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.Epigenetics · 2022Review
- Integrating the tumor-suppressive activity of Maspin with p53 in retuning the epithelial homeostasis: A working hypothesis and applicable prospects.Frontiers in oncology · 2022Review
- Gene-Targeted DNA Methylation: Towards Long-Lasting Reprogramming of Gene Expression?Advances in experimental medicine and biology · 2022Review
- Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Chromatin Manipulation and Editing: Challenges, New Technologies and Their Use in Plants.International journal of molecular sciences · 2021Review
- Epigenome engineering: new technologies for precision medicine.Nucleic acids research · 2020Article
- Transcriptional repression of PTEN in neural cells using CRISPR/dCas9 epigenetic editing.Scientific reports · 2020Article
- Innovative Precision Gene-Editing Tools in Personalized Cancer Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Review
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA hypermethylation is extensively explored as therapeutic target for gene expression modulation in cancer. Here, we re-activated hypermethylated candidate tumor suppressor genes (TSGs) (C13ORF18, CCNA1, TFPI2, and Maspin) by TET2-induced demethylation in cervical cancer cell lines. To redirect TET2 to hypermethylated TSGs, we engineered zinc finger proteins (ZFPs), which were first fused to the transcriptional activator VP64 to validate effective gene re-expression and confirm TSG function. ChIP-Seq not only revealed enriched binding of ZFPs to their intended sequence, but also considerable off-target binding, especially at promoter regions. Nevertheless, results obtained by targeted re-expression using ZFP-VP64 constructs were in line with cDNA overexpression; both revealed strong growth inhibition for C13ORF18 and TFPI2, but not for CCNA1 and Maspin. To explore effectivity of locus-targeted demethylation, ZFP-TET2 fusions were constructed which efficiently demethylated genes with subsequent gene re-activation. Moreover, targeting TET2 to TFPI2 and C13ORF18, but not CCNA1, significantly decreased cell growth, viability, and colony formation in cervical cancer cells compared to a catalytically inactive mutant of TET2. These data underline that effective re-activation of hypermethylated genes can be achieved through targeted DNA demethylation by TET2, which can assist in realizing sustained re-expression of genes of interest.
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