ArticleThe Journal of experimental medicine2013
The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 132 citations in OpenAlex.
- A tumor suppressor role of the miR-15b/16-2 cluster in T-cell acute lymphoblastic leukemia.Blood · 2026Article
- Reactivation of a TAL1 progenitor cell enhancer region by non-coding somatic variants in T-lineage acute lymphoblastic leukemia.bioRxiv : the preprint server for biology · 2026Article
- Reflecting on 30 years of miRNA biology in malignant hematology: current challenges and future directions.Blood advances · 2025Review
- Review
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- Review
- Article
- Transcriptional regulatory program controlled by MYB in T-cell acute lymphoblastic leukemia.Leukemia · 2024Article
- Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- The NF-κB1/p50 Subunit Influences the Notch/IL-6-Driven Expansion of Myeloid-Derived Suppressor Cells in Murine T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Article
- Notch3-regulated microRNAs impair CXCR4-dependent maturation of thymocytes allowing maintenance and progression of T-ALL.Oncogene · 2024Article
- MiR-223-3p in Cancer Development and Cancer Drug Resistance: Same Coin, Different Faces.International journal of molecular sciences · 2024Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Regulatory mechanisms and context-dependent roles of TAL1 in T-cell acute lymphoblastic leukemia.Haematologica · 2024Article
- Transcription Factor TAL1 in Erythropoiesis.Advances in experimental medicine and biology · 2024Review
- TAL1 hijacks MYCN enhancer that induces MYCN expression and dependence on mevalonate pathway in T-cell acute lymphoblastic leukemia.Leukemia · 2023Article
- MiRNA-related metastasis in oral cancer: moving and shaking.Cancer cell international · 2023Review
- Article
- The Role of FBXW7 in Gynecologic Malignancies.Cells · 2023Review
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 4 countries.
Funding
Abstract
The oncogenic transcription factor TAL1/SCL is aberrantly expressed in 60% of cases of human T cell acute lymphoblastic leukemia (T-ALL) and initiates T-ALL in mouse models. By performing global microRNA (miRNA) expression profiling after depletion of TAL1, together with genome-wide analysis of TAL1 occupancy by chromatin immunoprecipitation coupled to massively parallel DNA sequencing, we identified the miRNA genes directly controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. The most dynamically regulated miRNA was miR-223, which is bound at its promoter and up-regulated by the TAL1 complex. miR-223 expression mirrors TAL1 levels during thymic development, with high expression in early thymocytes and marked down-regulation after the double-negative-2 stage of maturation. We demonstrate that aberrant miR-223 up-regulation by TAL1 is important for optimal growth of TAL1-positive T-ALL cells and that sustained expression of miR-223 partially rescues T-ALL cells after TAL1 knockdown. Overexpression of miR-223 also leads to marked down-regulation of FBXW7 protein expression, whereas knockdown of TAL1 leads to up-regulation of FBXW7 protein levels, with a marked reduction of its substrates MYC, MYB, NOTCH1, and CYCLIN E. We conclude that TAL1-mediated up-regulation of miR-223 promotes the malignant phenotype in T-ALL through repression of the FBXW7 tumor suppressor.
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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.