ArticleCancer research2008
Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 216 citations in OpenAlex.
- MicroRNA expression and clinical outcomes in patients treated with adjuvant chemotherapy after complete resection of non-small cell lung carcinoma.Cancer research · 2010Trial
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- Cell Penetrating Thyclotides Facilitate Efficient Delivery of Bioactive Peptides into Cells.bioRxiv : the preprint server for biology · 2026Article
- Naphthoquinone-Amino Acids Regulate Cellular Cancer Associated Processes, p53 and miR-34a-5p Expression in Immortal and Tumorigenic Cervical Cell Lines.International journal of molecular sciences · 2026Article
- Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- MicroRNA-34a Mediates the Aldosterone-Induced Acceleration of Endothelial Senescence.International journal of hypertension · 2025Article
- Patient-derived organoids in non-small cell lung cancer: advances in drug sensitivity testing.Frontiers in pharmacology · 2025Review
- MiR-34b promotes oxidative stress and induces cellular senescence through TWIST1 in human cervical cancer.Translational oncology · 2024Article
- Comprehensive analysis of clinical and biological value ofWorld journal of gastrointestinal oncology · 2024Article
- Effects of Slow Freezing and Vitrification of Human Semen on Post-Thaw Semen Quality and miRNA Expression.International journal of molecular sciences · 2024Article
- The potential for senotherapy as a novel approach to extend life quality in veterinary medicine.Frontiers in veterinary science · 2024Review
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- Targeting Cell Cycle Facilitates E1A-Independent Adenoviral Replication.Journal of virology · 2023Article
- Correlation between Sperm Micro Ribonucleic Acid-34b and -34c Levels and Clinical Outcomes of Intracytoplasmic Sperm Injection in Men with Male Factor Infertility.International journal of molecular sciences · 2022Article
- Molecular mechanisms of inhibitor of growth (ING) family members in health and malignancy.Cancer cell international · 2022Review
- A miR-34a-guided, tRNACell death discovery · 2022Article
- Simultaneous regression and classification for drug sensitivity prediction using an advanced random forest method.Scientific reports · 2022Article
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- miRNA-Profiling in Ejaculated and Epididymal Pig Spermatozoa and Their Relation to Fertility after Artificial Insemination.Biology · 2022Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Nutlin-3, an MDM2 inhibitor, activates p53, resulting in several types of cancer cells undergoing apoptosis. Although p53 is mutated or deleted in approximately 50% of all cancers, p53 is still functionally active in the other 50%. Consequently, nutlin-3 and similar drugs could be candidates for neoadjuvant therapy in cancers with a functional p53. Cellular senescence is also a phenotype induced by p53 activation and plays a critical role in protecting against tumor development. In this report, we found that nutlin-3a can induce senescence in normal human fibroblasts. Nutlin-3a activated and repressed a large number of p53-dependent genes, including those encoding microRNAs. mir-34a, mir-34b, and mir-34c, which have recently been shown to be downstream effectors of p53-mediated senescence, were up-regulated, and inhibitor of growth 2 (ING2) expression was suppressed by nutlin-3a treatment. Two candidates for a p53-DNA binding consensus sequence were found in the ING2 promoter regulatory region; thus, we performed chromatin immunoprecipitation and electrophoretic mobility shift assays and confirmed p53 binding directly to those sites. In addition, the luciferase activity of a construct containing the ING2 regulatory region was repressed after p53 activation. Antisense knockdown of ING2 induces p53-independent senescence, whereas overexpression of ING2 induces p53-dependent senescence. Taken together, we conclude that nutlin-3a induces senescence through p53 activation in normal human fibroblasts, and p53-mediated mir34a, mir34b, and mir34c up-regulation and ING2 down-regulation may be involved in the senescence pathway.
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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.