ArticleGenes & development2014
A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.
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.
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Who cites it
170 citing papers in PubMed, 299 citations in OpenAlex.
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- Pan-cancer molecular signatures connecting aspartate transaminase to cancer prognosis, metabolic and immune signatures.Frontiers in oncology · 2026Article
- A Small Molecule Compound, Berberine Reduces IgE but Not IgG Production via Promoting miRNA-34a-p53 Axis.Cells · 2025Article
- The multifaceted role of microRNAs in colorectal cancer: pathogenesis and therapeutic implications.Non-coding RNA research · 2025Review
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- The emerging role of miRNAs in biological aging and age-related diseases.Non-coding RNA research · 2025Review
- A base editing platform for the correction of cancer driver mutations unmasks conserved p53 transcription programs.Genome biology · 2025Article
- Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis.Molecular therapy. Nucleic acids · 2025Article
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- Mitochondrial micro RNAs: Crucial players in carcinogenesis.Oncology research · 2025Review
- Nanocarriers: Exploring the Potential of Oligonucleotide Delivery.Current drug delivery · 2025Review
- Evidence for a TMAO-HULC-miRNA regulatory axis in colorectal cancer cells.International journal of molecular and cellular medicine · 2025Article
- A dataset of transcriptomic effects of camptothecin treatment on early zebrafish embryos.Data in brief · 2024Article
- MIR937 amplification potentiates ovarian cancer progression by attenuating FBXO16 inhibition on ULK1-mediated autophagy.Cell death & disease · 2024Article
- The Role of lncRNA-miR-26a-mRNA Network in Cancer Progression and Treatment.Biochemical genetics · 2024Review
- How MicroRNAs Command the Battle against Cancer.International journal of molecular sciences · 2024Review
- miR-34a is a tumor suppressor in zebrafish and its expression levels impact metabolism, hematopoiesis and DNA damage.PLoS genetics · 2024Article
- Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family.Biomedicines · 2024Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
As bona fide p53 transcriptional targets, miR-34 microRNAs (miRNAs) exhibit frequent alterations in many human tumor types and elicit multiple p53 downstream effects upon overexpression. Unexpectedly, miR-34 deletion alone fails to impair multiple p53-mediated tumor suppressor effects in mice, possibly due to the considerable redundancy in the p53 pathway. Here, we demonstrate that miR-34a represses HDM4, a potent negative regulator of p53, creating a positive feedback loop acting on p53. In a Kras-induced mouse lung cancer model, miR-34a deficiency alone does not exhibit a strong oncogenic effect. However, miR-34a deficiency strongly promotes tumorigenesis when p53 is haploinsufficient, suggesting that the defective p53-miR-34 feedback loop can enhance oncogenesis in a specific context. The importance of the p53/miR-34/HDM4 feedback loop is further confirmed by an inverse correlation between miR-34 and full-length HDM4 in human lung adenocarcinomas. In addition, human lung adenocarcinomas generate an elevated level of a short HDM4 isoform through alternative polyadenylation. This short HDM4 isoform lacks miR-34-binding sites in the 3' untranslated region (UTR), thereby evading miR-34 regulation to disable the p53-miR-34 positive feedback. Taken together, our results elucidated the intricate cross-talk between p53 and miR-34 miRNAs and revealed an important tumor suppressor effect generated by this positive feedback loop.
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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.