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Synthetic small inhibiting RNAs: Efficient tools to inactivate oncogenic mutations and restore p53 pathways
Open accessAbstract
Single base pair mutations that alter the function of tumor suppressor genes and oncogenes occur frequently during oncogenesis. The guardian of the genome, p53, is inactivated by point mutation in more than 50% of human cancers. Synthetic small inhibiting RNAs (siRNAs) can suppress gene expression in mammalian cells, although their degree of selectivity might be compromised by an amplification mechanism. Here, we demonstrate that a single base difference in siRNAs discriminates between mutant and WT p53 in cells expressing both forms, resulting in the restoration of WT protein function. Therefore, siRNAs may be used to suppress expression of point-mutated genes and provide the basis for selective and personalized antitumor therapy.
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“In 2002, a single base difference was found between wtp53 and mutp53, demonstrating that synthetic siRNAs are efficient tools to inactive oncogenic mutations and restore p53 pathways.573”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [573]
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MicroRNA targets in Drosophila
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Metadata
- Authors
- Martinez, L. A., Naguibneva, I., Lehrmann, H., Vervisch, A., Tchénio, T., Lozano, G., & Harel-Bellan, A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Scripps Research Institute (US)
- Unité Propre de Recherche 9079, Centre National de la Recherche Scientifique-Ligue Nationale Contre le Cancer, Service de Cytofluorométrie, Unité Propre de Recherche 1983, Centre National de la Recherche Scientifique, Institut André Lwoff, 7 Rue Guy Moquet, 94800 Villejuif, France; and University of Texas M. D. Anderson Cancer Center, Department of Molecular Genetics, Section of Cancer Genetics, 1515 Holcombe Boulevard, Houston, TX 77030
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-10-28
- Volume
- 99
- Issue
- 23
- Pages
- 14849-14854
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC137507
- OpenAlex
- W2017991840
- Cited by
- 210
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 8
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Philippe Foundation
- National Cancer Institute (CA09212502)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- siRNA, p53, point mutations, tumor suppressor, oncogenes, cancer therapy, precision oncology, gene expression inhibition
- MeSH terms
- Base Sequence, Humans, Mutation, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Point Mutation, RNA, Small Interfering
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