ArticleOncogene2018
The miR-106b-25 cluster mediates breast tumor initiation through activation of NOTCH1 via direct repression of NEDD4L.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 90 citations in OpenAlex.
- The SP1/NEDD4L Axis Suppresses the Breast Cancer Progression by Downregulating SNAI2 Expression.Biochemical genetics · 2026Article
- miR-106b-5p as a Central Regulator of Cancer Progression and Chemotherapy-Induced Cardiotoxicity: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Review
- The Role of MCM7 and Its Hosted miR-106b-25 Cluster in Renal Cancer Progression.International journal of molecular sciences · 2025Article
- The E3 Ligase NEDD4L Prevents Colorectal Cancer Liver Metastasis via Degradation of PRMT5 to Inhibit the AKT/mTOR Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NEDD4 signaling: a new frontier in the diagnosis and treatment of breast and ovarian cancers.Medical oncology (Northwood, London, England) · 2025Review
- Reversal of endocrine resistance via N6AMT1-NEDD4L pathway-mediated p110α degradation.Oncogene · 2025Article
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- Leveraging a disulfidptosis-based signature to characterize heterogeneity and optimize treatment in multiple myeloma.Frontiers in immunology · 2025Article
- NEDD4L Suppresses Proliferation and Promotes Apoptosis by Ubiquitinating RAC2 Expression and Acts as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2024Article
- Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis.International journal of molecular sciences · 2023Review
- Review
- miRNA-seq identification and clinical validation of CD138+ and circulating miR-25 in treatment response of multiple myeloma.Journal of translational medicine · 2023Article
- lncRNAProceedings of the National Academy of Sciences of the United States of America · 2023Article
- NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.Frontiers in pharmacology · 2023Review
- Integrative analysis of negatively regulated miRNA-mRNA axes for esophageal squamous cell carcinoma.Cancer biomarkers : section A of Disease markers · 2023Article
- NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation.Cancer biology & therapy · 2022Article
- Review
- Nanomaterial-assisted CRISPR gene-engineering - A hallmark for triple-negative breast cancer therapeutics advancement.Materials today. Bio · 2022Review
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- miR-106b as an emerging therapeutic target in cancer.Genes & diseases · 2022Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Tumor-initiating cells (TIC) represent a subset of tumor cells with increased self-renewal capability. TICs display resistance to frontline cancer treatment and retain the ability to repopulate a tumor after therapy, leading to cancer relapse. NOTCH signaling has been identified as an important driver of the TIC population, yet mechanisms governing regulation of this pathway in cancer remain to be fully elucidated. Here we identify a novel mechanism of NOTCH regulation and TIC induction in breast cancer via the miR-106b-25 miRNA cluster. We show that the miR-106b-25 cluster upregulates NOTCH1 in multiple breast cancer cell lines, representing both estrogen receptor (ER+) and triple negative breast cancer (TNBC) through direct repression of the E3 ubiquitin ligase, NEDD4L. We further show that upregulation of NOTCH1 is necessary for TIC induction downstream of miR-106b-25 in both ER + and TNBC breast cancer cells, and that re-expression of NEDD4L is sufficient to reverse miR106b-25-mediated NOTCH1 upregulation and TIC induction. Importantly, we demonstrate a significant positive correlation between miR-106b-25 and NOTCH1 protein, yet a significant inverse correlation between miR-106b-25 and NEDD4L mRNA in human breast cancer, suggesting a critical role for the miR106b-25/NEDD4L/NOTCH1 axis in the disease. Further, we show for the first time that NEDD4L expression alone is significantly associated with a better relapse-free prognosis for breast cancer patients. These data expand our knowledge of the mechanisms underlying NOTCH activation and TIC induction in breast cancer, and may provide new avenues for the development of therapies targeting this resistant subset of tumor cells.
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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.