ArticleJournal of translational medicine2014
Metallothionein III (MT3) is a putative tumor suppressor gene that is frequently inactivated in pediatric acute myeloid leukemia by promoter hypermethylation.
Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 46 citations in OpenAlex.
- Metallothionein Isoforms in Acute Myeloid Leukemia: Roles in Survival, Differentiation, and Stress Adaptation.Hematology reports · 2026Review
- Zinc-binding protein metallothionein 3 protects vascular smooth muscle cells from ferroptosis via blocking lysosomal degradation of GPX4.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Emerging Roles of Metallothioneins in Human Pathophysiology: A Review.Health science reports · 2025Article
- Article
- Decoding the Implications of Zinc in the Development and Therapy of Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Identification of SLC22A17 DNA methylation hotspot as a potential biomarker in cutaneous melanoma.Journal of translational medicine · 2024Article
- Metallothionein 3 Potentiates Pulmonary Artery Smooth Muscle Cell Proliferation by Promoting Zinc-MTF1-ATG5 Axis-mediated Autophagosome Formation.International journal of biological sciences · 2024Article
- Identification of ferroptosis-related genes for overall survival prediction in hepatocellular carcinoma.Scientific reports · 2022Article
- Construction of a Novel Oxidative Stress Response-Related Gene Signature for Predicting the Prognosis and Therapeutic Responses in Hepatocellular Carcinoma.Disease markers · 2022Article
- Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells.Oncology reports · 2020Article
- Metallothionein-3 as a multifunctional player in the control of cellular processes and diseases.Molecular brain · 2020Review
- Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide.ACS omega · 2020Article
- miR-325-3p Overexpression Inhibits Proliferation and Metastasis of Bladder Cancer Cells by Regulating MT3.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- A role of metallothionein-3 in radiation-induced autophagy in glioma cells.Scientific reports · 2020Article
- Co-occurrence and Mutual Exclusivity Analysis of DNA Methylation Reveals Distinct Subtypes in Multiple Cancers.Frontiers in cell and developmental biology · 2020Article
- Article
- Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells.International journal of molecular sciences · 2019Article
- The roles of metallothioneins in carcinogenesis.Journal of hematology & oncology · 2018Review
- Integrated epigenetic and genetic analysis identifies markers of prognostic significance in pediatric acute myeloid leukemia.Oncotarget · 2018Article
- Metallothioneins: Emerging Modulators in Immunity and Infection.International journal of molecular sciences · 2017Review
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute myeloid leukemia (AML) is the second most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature in various tumors, including AML. Metallothionein III (MT3) is a tumor suppresser reported to show promoter hypermethylated in various cancers. However, the expression and molecular function of MT3 in pediatric AML is unclear.
methodsEleven human leukemia cell lines and 41 pediatric AML samples and 20 NBM/ITP (Norma bone marrow/Idiopathic thrombocytopenic purpura) control samples were analyzed. Transcription levels of MT3 were evaluated by semi-quantitative and real-time PCR. MT3 methylation status was determined by methylation specific PCR (MSP) and bisulfite genomic sequencing (BSG). The molecular mechanism of MT3 was investigated by apoptosis assays and PCR array analysis.
resultsThe MT3 promoter was hypermethylated in leukemia cell lines. More CpG's methylated of MT3 was observed 39.0% pediatric AML samples compared to 10.0% NBM controls. Transcription of MT3 was also significantly decreased in AML samples compared to NBM/ITP controls (P < 0.001); patients with methylated MT3 exhibited lower levels of MT3 expression compared to those with unmethylated MT3 (P = 0.049). After transfection with MT3 lentivirus, proliferation was significantly inhibited in AML cells in a dose-dependent manner (P < 0.05). Annexin V assay showed that apoptosis was significantly upregulated MT3-overexpressing AML cells compared to controls. Real-time PCR array analysis revealed 34 dysregulated genes that may be implicated in MT3 overexpression and apoptosis in AML, including FOXO1.
conclusionMT3 may be a putative tumor suppressor gene in pediatric AML. Epigenetic inactivation of MT3 via promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Overexpression of MT3 may inhibit proliferation and induce apoptosis in AML cells. FOXO1 was dysregulated in MT3-overexpressing cells, offering an insight into the mechanism of MT3-induced apoptosis. However, further research is required to determine the underlying molecular details.
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