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Updated: Aug 13, 2025

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
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E3 Ubiquitin Ligase NEDD4 Affects Estrogen Receptor α Expression and the Prognosis of Patients with Hormone

Yutaka Natori1, Junko Suga1, Emi Tokuda1

  • 1Department of Medical Oncology, Fukushima Medical University, Fukushima 960-1295, Japan.

Cancers
|January 21, 2023
PubMed

Insights

Low expression of Neural precursor cell-expressed developmentally downregulated 4-1 (NEDD4) correlates with better outcomes in hormone receptor-positive breast cancer. Lower NEDD4 levels improve disease-free and overall survival by increasing estrogen receptor α sensitivity to hormone therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Neural precursor cell-expressed developmentally downregulated 4-1 (NEDD4) is an E3 ligase involved in protein degradation.
  • Estrogen receptor α (ERα) is a key target in hormone receptor-positive breast cancer treatment.
  • NEDD4's role in breast cancer prognosis and ERα regulation requires further elucidation.

Purpose of the Study:

  • To investigate the association between NEDD4 expression levels and clinical outcomes in early breast cancer patients.
  • To explore the mechanistic link between NEDD4, ERα expression, and response to hormone therapy.

Main Methods:

  • Retrospective cohort study of 143 hormone receptor-positive, HER2-negative early breast cancer patients.
  • Analysis of NEDD4 mRNA levels (high vs. low groups) and correlation with survival data.
  • Western blotting and cell culture experiments to assess ERα expression and cell proliferation in response to NEDD4 knockdown and hormone therapy.

Main Results:

  • Patients with low NEDD4 mRNA levels exhibited significantly longer disease-free survival (p=0.048) and overall survival (p=0.022) compared to those with high NEDD4 levels.
  • NEDD4 knockdown in breast cancer cells led to increased ERα expression.
  • NEDD4-knockdown cells showed suppressed proliferation when treated with tamoxifen or estradiol deprivation, indicating enhanced sensitivity to hormone therapy.

Conclusions:

  • Low NEDD4 expression is associated with a better prognosis in hormone receptor-positive breast cancer.
  • NEDD4 regulates ERα stability, and its knockdown enhances breast cancer cell sensitivity to endocrine treatments.
  • Targeting NEDD4 or understanding its role may offer new therapeutic strategies for breast cancer.
Keywords:
NEDD4estrogen receptorhormone receptor-positive breast cancerhormone therapyretrospective cohort study

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