ArticleOncogene2015
Involvement of G-quadruplex structures in regulation of human RET gene expression by small molecules in human medullary thyroid carcinoma TT cells.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Synthetic G-quadruplex components for predictable, precise two-level control of mammalian recombinant protein expression.Nucleic acids research · 2025Article
- A novel role for nonactin: interfering with G-quadruplex in RET-driven medullary thyroid cancer.BMC cancer · 2024Article
- Stable bulged G-quadruplexes in the human genome: identification, experimental validation and functionalization.Nucleic acids research · 2023Article
- Adefovir Dipivoxil as a Therapeutic Candidate for Medullary Thyroid Carcinoma: Targeting RET and STAT3 Proto-Oncogenes.Cancers · 2023Article
- Article
- Quadruplex Ligands in Cancer Therapy.Cancers · 2021Review
- An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer.International journal of molecular sciences · 2020Review
- Inhibition of p53 DNA binding by a small molecule protects mice from radiation toxicity.Oncogene · 2020Article
- The Oncogenic Signaling Pathways inCells · 2019Article
- Bulged and Canonical G-Quadruplex Conformations Determine NDPK Binding Specificity.Molecules (Basel, Switzerland) · 2019Article
- Promise of G-Quadruplex Structure Binding Ligands as Epigenetic Modifiers with Anti-Cancer Effects.Molecules (Basel, Switzerland) · 2019Review
- Naphthalene Diimides as Multimodal G-Quadruplex-Selective Ligands.Molecules (Basel, Switzerland) · 2019Review
- Characterization of clinically used oral antiseptics as quadruplex-binding ligands.Nucleic acids research · 2018Article
- Novel splicing in IGFN1 intron 15 and role of stable G-quadruplex in the regulation of splicing in renal cell carcinoma.PloS one · 2018Article
- SVA retrotransposons as potential modulators of neuropeptide gene expression.Neuropeptides · 2017Review
- Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative.International journal of oncology · 2017Article
- The Consequences of Overlapping G-Quadruplexes and i-Motifs in the Platelet-Derived Growth Factor Receptor β Core Promoter Nuclease Hypersensitive Element Can Explain the Unexpected Effects of Mutations and Provide Opportunities for Selective Targeting of Both Structures by Small Molecules To Downregulate Gene Expression.Journal of the American Chemical Society · 2017Article
- High-resolution three-dimensional NMR structure of theThe Journal of biological chemistry · 2017Article
- Permanganate/S1 Nuclease Footprinting Reveals Non-B DNA Structures with Regulatory Potential across a Mammalian Genome.Cell systems · 2017Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The RET (rearranged during transfection) proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signaling molecules. The activating germline point mutations in the RET, which are known to induce oncogenic activation of RET tyrosine kinase, are associated with the development of medullary thyroid carcinoma (MTC) and pathogenesis of multiple endocrine neoplasia type 2 (MEN2). The polypurine/polypyrimidine tract in the proximal promoter region of the human RET gene (-51 to -33 relative to transcription start site) is essential for basal transcriptional activity of this gene. This tract consists of a guanine-rich sequence containing five runs of at least three contiguous guanines separated by one or more bases, conforming to a general motif capable of forming an intramolecular G-quadruplex. Here, we show that specific G-quadruplex structures formed in the RET promoter region act to repress the transcription of this gene, and transcription of this gene can be controlled by ligand-mediated G-quadruplex stabilization. In this study, NSC194598, a derivative of indeno[1,2,3-de]quinazoline, was found to be a novel G-quadruplex interactive agent that interfered with transcriptional activation of mutated RET gene in human medullary thyroid carcinoma TT cells. This compound significantly reduced endogenous RET protein levels and increased apoptosis in these cells. Our results provide further support for the idea that G-quadruplex structures may have a critical role in transcriptional regulation of the RET gene in vivo, providing insight into a novel strategy for transcriptional repression of this gene by small molecules.
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