Estrogen receptor alpha mutations regulate gene expression and cell growth in breast cancer through microRNAs

Spencer Arnesen1, Jacob T Polaski1, Zannel Blanchard1

  • 1Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.

NAR Cancer
|June 5, 2023
PubMed

Insights

Mutant estrogen receptor alpha (ER) in breast cancer affects gene expression through microRNAs. These microRNAs target key genes, influencing cell growth and offering new therapeutic targets for ER-positive metastatic breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Estrogen receptor alpha (ER) mutations are found in up to 30% of metastatic ER-positive breast cancers.
  • Mutant ER impacts thousands of genes, with some regulatory mechanisms remaining unexplained, suggesting post-transcriptional roles.

Purpose of the Study:

  • To investigate the role of microRNAs in gene regulation driven by mutant ER.
  • To identify microRNAs dysregulated in ER mutant cells and their impact on cellular processes.

Main Methods:

  • Identification of dysregulated microRNAs in ER mutant cells.
  • Analysis of microRNA targets among mutant-specific genes.
  • Functional studies using microRNA mimics and inhibitors to assess effects on gene expression and proliferation.
  • In-depth evaluation of miR-301b and its role in ER mutant cell proliferation.

Main Results:

  • Several microRNAs were found to be dysregulated in ER mutant cells.
  • These microRNAs target a significant number of mutant-specific genes involved in critical cellular functions.
  • Modulating microRNA activity altered gene expression and proliferation in ER mutant cells.
  • miR-301b was identified to play a key role in the proliferation of ER mutant cells, involving PRKD3.

Conclusions:

  • MicroRNAs are significant contributors to mutant ER-mediated gene regulation in breast cancer.
  • Dysregulated microRNAs play a role in the cellular effects of mutant ER, impacting proliferation.
  • Targeting microRNAs presents a potential therapeutic strategy for ER-positive metastatic breast cancer with ER mutations.

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