ArticleMolecular oncology2019
Mutual regulation of MDM4 and TOP2A in cancer cell proliferation.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 44 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 81 citations in OpenAlex.
- Phillyrin regulates the JAK2/STAT3 signaling pathway by inhibiting TOP2A expression to accelerate ferroptosis in hepatocellular carcinoma.Oncology reports · 2025Article
- Intratumoral Heterogeneity and Immune Microenvironment in Hepatoblastoma Revealed by Single-Cell RNA Sequencing.Journal of cellular and molecular medicine · 2025Article
- Article
- Multi-omics analysis reveals the panoramic picture of TOP2A in pan-cancer.Scientific reports · 2025Article
- Exploring the anti-gastric cancer mechanisms of Diosgenin through integrated network analysis, bioinformatics, single-cell sequencing, and cell experiments.Frontiers in pharmacology · 2025Article
- TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.Cancer biology & therapy · 2024Article
- Multiple Myeloma: Genetic and Epigenetic Biomarkers with Clinical Potential.International journal of molecular sciences · 2024Article
- Integrated bioinformatics reveals genetic links between visceral obesity and uterine tumors.Molecular genetics and genomics : MGG · 2024Article
- Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.International journal of molecular sciences · 2024Article
- Long noncoding RNA MALAT-1: A versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance.Non-coding RNA research · 2024Review
- Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.Cell death and differentiation · 2024Article
- MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers.European journal of medical research · 2024Article
- Cellular carcinogenesis in preleukemic conditions:drivers and defenses.Fukushima journal of medical science · 2024Review
- Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications.Cancers · 2023Review
- Identification of cervical cancer stem cells using single-cell transcriptomes of normal cervix, cervical premalignant lesions, and cervical cancer.EBioMedicine · 2023Article
- miR-30c-2-3p suppresses the proliferation of human renal cell carcinoma cells by targeting TOP2A.Asian biomedicine : research, reviews and news · 2023Article
- Identification of ferroptosis and drug resistance related hub genes to predict the prognosis in Hepatocellular Carcinoma.Scientific reports · 2023Article
- Targeting long non-coding RNA MALAT1 reverses cancerous phenotypes of breast cancer cells through microRNA-561-3p/TOP2A axis.Scientific reports · 2023Article
- Circular RNA Ubiquitin-associated Protein 2 Silencing Suppresses Bladder Cancer Progression by Downregulating DNA Topoisomerase 2-alpha Through Sponging miR-496.European urology open science · 2023Article
- High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer.BMC urology · 2023Article
Corrections and comments
- Retraction · 2024-12-03Concerns/Issues about Image · Duplication of/in Image · Investigation by Journal/Publisher · Investigation by Third Party · Original Data and/or Images not Provided and/or not Available · Unreliable Data · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
MDM4 and topoisomerase IIα (TOP2A) are overexpressed in various human cancers. MDM4 acts as an oncoprotein which promotes cancer progression by inhibiting tumor suppressor p53. As a DNA replication- and cell division-regulating enzyme, TOP2A is the main target of many anticancer therapy regimens; however, the exact role of TOP2A in cancer remains elusive. Herein, we report that MDM4 and TOP2A bind to each other and are mutually upregulated at the post-translational level, leading to TOP2A protein stabilization, inhibition of p53, and increased tumor-cell proliferation. We demonstrate that the C-terminal region (CTR) of TOP2A binds to a unique sequence (residues: 188-238) of MDM4, which contains an auto-inhibitory segment regulating the MDM4-p53 interaction. TOP2A binding in turn activates MDM4 for p53 binding, resulting in enhanced inhibition of p53 and cancer cell proliferation. Conversely, binding of the MDM4 sequence to the CTR of TOP2A stabilizes TOP2A protein, leading to increased TOP2A protein expression. These results reveal novel functions of MDM4 and TOP2A as well as their interactions in oncogenesis, suggesting that inhibition of the MDM4-TOP2A interaction may represent a novel strategy in specifically and simultaneously targeting TOP2A and MDM4 for cancer treatment.
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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.