Related Experiment Video

Updated: May 24, 2025

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

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Upregulation of miR-99b-5p Modulates ESR1 Expression as an Adaptive Mechanism to Circumvent Drug Response via

Senem Noyan1, Bala Gür Dedeoğlu1

  • 1Biotechnology Institute, Ankara University, Ankara, Türkiye.

Balkan Medical Journal
|March 4, 2025
PubMed
Abstract

Insights

MicroRNA-99b-5p overexpression drives endocrine therapy resistance in ER+ breast cancer by promoting ER-HER2/EGFR crosstalk. Inhibiting miR-99b-5p restores drug sensitivity, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Endocrine resistance is a major challenge in estrogen receptor-positive (ER+) breast cancer.
  • Estrogen receptor (ER) and HER family receptor crosstalk (HER2, EGFR) drives resistance to tamoxifen and trastuzumab.
  • Dysregulated microRNAs (miRNAs) are implicated in therapy response.

Purpose of the Study:

  • To investigate the role of miR-99b-5p in ER-HER2/EGFR crosstalk.
  • To determine miR-99b-5p's impact on therapy resistance in ER+ breast cancer cells.

Main Methods:

  • Analyzed miR-99b-5p expression and prognostic significance in breast cancer using TCGA data.
  • Transfected BT-474 cells with miR-99b-5p mimics/inhibitors.
  • Assessed cell proliferation and ER-HER2/EGFR signaling pathway activation after drug treatment (tamoxifen, trastuzumab).
  • Quantified protein levels (EGFR, HER2, ESR1) via Western blotting.

Main Results:

  • miR-99b-5p was overexpressed in tumors, correlating with poor survival and enhanced ER signaling.
  • miR-99b-5p mimics increased ESR1 expression and proliferation, conferring resistance to tamoxifen/trastuzumab.
  • miR-99b-5p inhibition restored drug sensitivity and reduced proliferation.

Conclusions:

  • miR-99b-5p is a key regulator of endocrine and HER2-targeted therapy resistance in ER+ breast cancer.
  • Targeting miR-99b-5p presents a potential therapeutic strategy for ER+/HER2+ breast cancer.
  • Further research is needed to validate miR-99b-5p inhibition in clinical settings.

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