ArticleOncotarget2016
Allele-specific silencing of mutant p53 attenuates dominant-negative and gain-of-function activities.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- The Prolonged Half-Life of the p53 Missense Variant R248Q Promotes Accumulation and Heterotetramer Formation with Wild-Type p53 to Exert the Dominant-Negative Effect.Cancer research · 2025Article
- Therapeutic potential of combating cancer by restoring wild-type p53 through mRNA nanodelivery.Nanomedicine : nanotechnology, biology, and medicine · 2024Review
- Long noncoding RNA LINC01088 inhibits esophageal squamous cell carcinoma progression by targeting the NPM1-HDM2-p53 axis.Acta biochimica et biophysica Sinica · 2023Article
- Review
- Emerging Pharmacotherapeutic Strategies to Overcome Undruggable Proteins in Cancer.International journal of biological sciences · 2023Review
- DNAJA1- and conformational mutant p53-dependent inhibition of cancer cell migration by a novel compound identified through a virtual screen.Cell death discovery · 2022Article
- Mutant p53 Depletion by Novel Inhibitors for HSP40/J-Domain Proteins Derived from the Natural Compound Plumbagin.Cancers · 2022Article
- TP53 in Myelodysplastic Syndromes.Cancers · 2021Review
- TP53 in Biology and Treatment of Osteosarcoma.Cancers · 2021Review
- Article
- Suppression of HSF1 activity by wildtype p53 creates a driving force for p53 loss-of-heterozygosity.Nature communications · 2021Article
- The Rich World of p53 DNA Binding Targets: The Role of DNA Structure.International journal of molecular sciences · 2019Review
- TP53 in bone and soft tissue sarcomas.Pharmacology & therapeutics · 2019Review
- Regulators of Oncogenic Mutant TP53 Gain of Function.Cancers · 2018Review
- The interplay between mutant p53 and the mevalonate pathway.Cell death and differentiation · 2018Review
- Article
- Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others.Nature reviews. Clinical oncology · 2018Review
- Control of Nucleotide Metabolism Enables Mutant p53's Oncogenic Gain-of-Function Activity.International journal of molecular sciences · 2017Review
- ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy.G3 (Bethesda, Md.) · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Many p53 hotspot mutants not only lose the transcriptional activity, but also show dominant-negative (DN) and oncogenic gain-of-function (GOF) activities. Increasing evidence indicates that knockdown of mutant p53 (mutp53) in cancer cells reduces their aggressive properties, suggesting that survival and proliferation of cancer cells are, at least partially, dependent on the presence of mutp53. However, these p53 siRNAs can downregulate both wild-type p53 (wtp53) and mutp53, which limits their therapeutic applications. In order to specifically deplete mutp53, we have developed allele-specific siRNAs against p53 hotspot mutants and validated their biological effects in the absence or presence of wtp53. First, the mutp53-specific siRNAs selectively reduced protein levels of matched p53 mutants with minimal reduction in wtp53 levels. Second, downregulation of mutp53 in cancer cells expressing a mutp53 alone (p53mut) resulted in significantly decreased cell proliferation and migration. Third, transfection of mutp53-specific siRNAs in cancer cells expressing both wtp53 and mutp53 also reduced cell proliferation and migration with increased transcripts of p53 downstream target genes, which became further profound when cells were treated with an MDM2 inhibitor Nutlin-3a or a chemotherapeutic agent doxorubicin. These results indicate that depletion of mutp53 by its specific siRNA restored endogenous wtp53 activity in cells expressing both wtp53 and mutp53. This is the first study demonstrating biological effects and therapeutic potential of allele-specific silencing of mutp53 by mutp53-specific siRNAs in cancer cells expressing both wtp53 and mutp53, thus providing a novel strategy towards targeted cancer therapies.
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What OpenQuestion holds
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.