MiRNA-27a sensitizes breast cancer cells to treatment with Selective Estrogen Receptor Modulators

Bojan Ljepoja1, Jonathan García-Roman1, Ann-Katrin Sommer1

  • 1Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany.

Abstract

Insights

MicroRNA-27a (miR-27a) enhances sensitivity to endocrine therapies in ER-positive breast cancer by upregulating ERα. High miR-27a levels correlate with improved patient survival following SERM treatment.

Area of Science:

  • Molecular Oncology
  • Non-coding RNA Biology
  • Breast Cancer Research

Background:

  • MicroRNA-27a (miR-27a) is implicated in various cancers, including regulating estrogen receptor alpha (ERα) in breast cancer.
  • Estrogen receptor-positive (ERα-positive) tumors are often treated with Selective Estrogen Receptor Modulators (SERMs).

Purpose of the Study:

  • To investigate the role of miR-27a in response to SERM treatment in breast cancer.
  • To elucidate the relationship between miR-27a and ERα signaling in endocrine therapy resistance.

Main Methods:

  • Generated tamoxifen-resistant breast cancer cell lines (MCF7, T47D) via molecular evolution.
  • Utilized miR-27a mimics and ERα modulation, with analyses including RT-qPCR, western blotting, and ERE-reporter assays.
  • Assessed SERM treatment response (tamoxifen, endoxifen, toremifene) via cell viability and apoptosis assays, alongside in silico survival analysis of METABRIC data.

Main Results:

  • Tamoxifen-resistant cells exhibited reduced ERα and miR-27a expression.
  • Overexpression of miR-27a increased ERα levels; ERα modulation decreased miR-27a expression, indicating a positive feedback loop.
  • Elevated miR-27a expression enhanced sensitivity to SERMs and re-sensitized cells to tamoxifen, correlating with improved survival in luminal A breast cancer patients.

Conclusions:

  • MiR-27a sensitizes luminal A breast cancer cells to SERM treatments through a positive feedback loop with ERα.
  • High miR-27a expression is associated with increased overall survival in ER-positive breast cancer patients undergoing endocrine therapy.

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