ArticleOncotarget2016
Waking up dormant tumor suppressor genes with zinc fingers, TALEs and the CRISPR/dCas9 system.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 88 citations in OpenAlex.
- Designing and testing CRISPRi-based synthetic gene circuits in plants.Nature protocols · 2026Review
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- Tumor suppressor network dysregulation in neuroblastoma: molecular mechanisms and precision therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Reprimo (RPRM): A Tumor Suppressor That Induces Extrinsic Apoptosis via YAP Signaling.Cancer science · 2025Review
- PTEN defects in cancer, from gene to protein molecular causes and therapeutic targets.Discover oncology · 2025Review
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- Extrinsic induction of apoptosis and tumor suppression via the p53-Reprimo-Hippo-YAP/TAZ-p73 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Harnessing the evolving CRISPR/Cas9 for precision oncology.Journal of translational medicine · 2024Review
- Effects of DNA methylation and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2024Review
- Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy.Molecular cancer · 2024Review
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.Frontiers in genome editing · 2024Review
- Current Approaches to Epigenetic Therapy.Epigenomes · 2023Review
- Synthetic Epigenetic Reprogramming of Mesenchymal to Epithelial States Using the CRISPR/dCas9 Platform in Triple Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- 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
- Strategies to target the cancer driver MYC in tumor cells.Frontiers in oncology · 2023Review
- Design, Construction, and Validation of Targeted Gene Activation with TREE System in Human Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The aberrant epigenetic silencing of tumor suppressor genes (TSGs) plays a major role during carcinogenesis and regaining these dormant functions by engineering of sequence-specific epigenome editing tools offers a unique opportunity for targeted therapies. However, effectively normalizing the expression and regaining tumor suppressive functions of silenced TSGs by artificial transcription factors (ATFs) still remains a major challenge. Herein we describe novel combinatorial strategies for the potent reactivation of two class II TSGs, MASPIN and REPRIMO, in cell lines with varying epigenetic states, using the CRISPR/dCas9 associated system linked to a panel of effector domains (VP64, p300, VPR and SAM complex), as well as with protein-based ATFs, Zinc Fingers and TALEs. We found that co-delivery of multiple effector domains using a combination of CRISPR/dCas9 and TALEs or SAM complex maximized activation in highly methylated promoters. In particular, CRISPR/dCas9 VPR with SAM upregulated MASPIN mRNA (22,145-fold change) in H157 lung cancer cells, with accompanying re-expression of MASPIN protein, which led to a concomitant inhibition of cell proliferation and induction of apoptotic cell death. Consistently, CRISPR/dCas9 VP64 with SAM upregulated REPRIMO (680-fold change), which led to phenotypic reprogramming in AGS gastric cancer cells. Altogether, our results outlined novel sequence-specific, combinatorial epigenome editing approaches to reactivate highly methylated TSGs as a promising therapy for cancer and other diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.