ArticleBlood2009
Specific activation of microRNA106b enables the p73 apoptotic response in chronic lymphocytic leukemia by targeting the ubiquitin ligase Itch for degradation.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 82 citations in OpenAlex.
- MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia.Molecular cancer · 2010Trial
- Harnessing TP73‑targeted nintedanib: A novel strategy to halt triple‑negative breast cancer via p53‑PPARα/PI3K‑Akt pathway suppression.International journal of oncology · 2025Article
- Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study.International journal of molecular sciences · 2023Article
- P63 and P73 Activation in Cancers with p53 Mutation.Biomedicines · 2022Review
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies.Discover oncology · 2021Review
- The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis.Translational cancer research · 2021Article
- Targeting Post-Translational Modifications of the p73 Protein: A Promising Therapeutic Strategy for Tumors.Cancers · 2021Review
- Review
- The Risks of miRNA Therapeutics: In a Drug Target Perspective.Drug design, development and therapy · 2021Review
- ITCH as a potential therapeutic target in human cancers.Seminars in cancer biology · 2020Review
- The Role of Noncoding RNAs in B-Cell Lymphoma.Frontiers in oncology · 2020Review
- Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity.International journal of molecular sciences · 2019Review
- Differential Sensitivity of Target Genes to Translational Repression by miR-17~92.PLoS genetics · 2017Article
- Article
- HDAC Inhibition Induces MicroRNA-182, which Targets RAD51 and Impairs HR Repair to Sensitize Cells to Sapacitabine in Acute Myelogenous Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Association of tumour microRNA profiling with outcomes in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy.British journal of cancer · 2016Article
- An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model.Oncotarget · 2016Article
- MiR-106b exhibits an anti-angiogenic function by inhibiting STAT3 expression in endothelial cells.Lipids in health and disease · 2016Article
- Negative correlation of ITCH E3 ubiquitin ligase and miRNA-106b dictates metastatic progression in pancreatic cancer.Oncotarget · 2016Article
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10 authors at 2 institutions in 1 country.
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Abstract
Chronic lymphocytic leukemia (CLL) is characterized by cells that exhibit dysfunctional apoptosis. Here, we show that deacetylase inhibition led to the E2F1- and myc-mediated transcriptional activation of the microRNA miR106b in primary CLL cells. Induction of miR106b was associated with a down-regulation in the levels of the E3-ubiquitin ligase Itch. Decreases in Itch protein levels were associated with a reciprocal accumulation of its proapoptotic substrate, TAp73 (p73), and induction of p53 up-regulated modulator of apoptosis (PUMA) mRNA and protein. This event was accompanied by mitochondrial dysfunction, processing of caspase-9, and apoptosis of CLL cells. Ectopic expression of miR106b in CLL cells demonstrated that Itch was a direct target of miR106b such that miR106b-induced decreases in Itch resulted in an accumulation of p73. Thus, our results identify a novel regulatory mechanism wherein microRNA regulate cell survival by mediating the posttranscriptional down-regulation of an ubiquitin ligase, leading to the induction of a proapoptotic regulator in malignant cells. Silencing of miRNA expression in CLL may selectively suppress proapoptotic pathways, providing such tumors with a survival advantage. Consequently, chemotherapeutic drugs that activate miR106b could initiate a p53-independent mechanism that targets CLL cells.
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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.