ArticlePloS one2012
MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Rs4938723 Polymorphism Is Associated with Susceptibility to Hepatocellular Carcinoma Risk and Is a Protective Factor in Leukemia, Colorectal, and Esophageal Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2018Pooled it
- Non-Coding RNAs in Breast Cancer: Diagnostic and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Patient-matched tumours, plasma, and cell lines reveal tumour microenvironment- and cell culture-specific microRNAs.Biology open · 2024Article
- miR-34a is a tumor suppressor in zebrafish and its expression levels impact metabolism, hematopoiesis and DNA damage.PLoS genetics · 2024Article
- Quinazoline sulfonamide derivatives targeting MicroRNA-34a/MDM4/p53 apoptotic axis with radiosensitizing activity.Future medicinal chemistry · 2024Article
- Review
- Gentamycin Rationally Repositioned to Inhibit miR-34a Ameliorates Oxidative Injury to PC12 Cells.ACS omega · 2023Article
- Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- MDM4 alternative splicing and implication in MDM4 targeted cancer therapies.American journal of cancer research · 2021Review
- A feedback circuit of miR-34a/MDM4/p53 regulates apoptosis in chronic lymphocytic leukemia cells.Translational cancer research · 2020Article
- Multifunctional Roles of miR-34a in Cancer: A Review with the Emphasis on Head and Neck Squamous Cell Carcinoma and Thyroid Cancer with Clinical Implications.Diagnostics (Basel, Switzerland) · 2020Review
- DNA methylation and miRNA-1296 act in concert to mediate spatiotemporal expression of KPNA7 during bovine oocyte and early embryonic development.BMC developmental biology · 2019Article
- Advances and challenges in studying noncoding RNA regulation of drug metabolism and development of RNA therapeutics.Biochemical pharmacology · 2019Review
- Innate extracellular vesicles from melanoma patients suppress β-catenin in tumor cells by miRNA-34a.Life science alliance · 2019Article
- The long and the short of it: the MDM4 tail so far.Journal of molecular cell biology · 2019Review
- Integrative analysis reveals disrupted pathways regulated by microRNAs in cancer.Nucleic acids research · 2018Article
- Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.International journal of molecular sciences · 2018Article
- MiR-370 promotes apoptosis in colon cancer by directly targeting MDM4.Oncology letters · 2018Article
- A comprehensive investigation using meta-analysis and bioinformatics on miR-34a-5p expression and its potential role in head and neck squamous cell carcinoma.American journal of translational research · 2018Article
- Quantum Dot Based Nano-Biosensors for Detection of Circulating Cell Free miRNAs in Lung Carcinogenesis: From Biology to Clinical Translation.Frontiers in genetics · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMDM4, also called MDMX or HDMX in humans, is an important negative regulator of the p53 tumor suppressor. MDM4 is overexpressed in about 17% of all cancers and more frequently in some types, such as colon cancer or retinoblastoma. MDM4 is known to be post-translationally regulated by MDM2-mediated ubiquitination to decrease its protein levels in response to genotoxic stress, resulting in accumulation and activation of p53. At the transcriptional level, MDM4 gene regulation has been less clearly understood. We have reported that DNA damage triggers loss of MDM4 mRNA and a concurrent increase in p53 activity. These experiments attempt to determine a mechanism for down-regulation of MDM4 mRNA. METHODOLOGY/PRINCIPAL
findingsHere we report that MDM4 mRNA is a target of hsa-mir-34a (miR-34a). MDM4 mRNA contains a lengthy 3' untranslated region; however, we find that it is a miR-34a site within the open reading frame (ORF) of exon 11 that is responsible for the repression. Overexpression of miR-34a, but not a mutant miR-34a, is sufficient to decrease MDM4 mRNA levels to an extent identical to those of known miR-34a target genes. Likewise, MDM4 protein levels are decreased by miR-34a overexpression. Inhibition of endogenous miR-34a increased expression of miR-34a target genes and MDM4. A portion of MDM4 exon 11 containing this 8mer-A1 miR-34a site fused to a luciferase reporter gene is sufficient to confer responsiveness, being inhibited by additional expression of exogenous mir-34a and activated by inhibition of miR-34a. CONCLUSIONS/SIGNIFICANCE: These data establish a mechanism for the observed DNA damage-induced negative regulation of MDM4 and potentially provide a novel means to manipulate MDM4 expression without introducing DNA damage.
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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.