Synthetic small inhibiting RNAs: Efficient tools to inactivate oncogenic mutations and restore p53 pathways
| Autor: | Irina Naguibneva, Thierry Tchénio, Annick Harel-Bellan, Arlette Vervisch, Luis Martinez, Heike Lehrmann, Guillermina Lozano |
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| Rok vydání: | 2002 |
| Předmět: |
Small interfering RNA
Mutation Multidisciplinary Base Sequence Point mutation Mutant Biological Sciences Biology Genes p53 medicine.disease_cause Gene Expression Regulation Neoplastic Gene expression Cancer research medicine Humans Point Mutation RNA Small Interfering Tumor Suppressor Protein p53 Carcinogenesis Gene Suppressor mutation |
| Zdroj: | Proceedings of the National Academy of Sciences. 99:14849-14854 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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