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Updated: Feb 2, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
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.
Background:
MicroRNA-27a (miR-27a) is a small non-coding RNA, shown to play a role in multiple cancers, including the regulation of ERα expression in breast cancer. Most ERα positive tumors are treated with Selective Estrogen Receptor Modulators (SERMs) and thus the role of miR-27a expression in response to SERM treatment is of interest.
Methods:
Tamoxifen resistant cells were generated by molecular evolution with six cycles of tamoxifen treatment. MCF7 and T47D luminal A breast cancer cell lines were either treated with miR-27a mimics, or ER-signaling was modulated ectopically. The changes were analyzed with RT-qPCR, western blotting and transcriptional activity ERE-reporter assays. Moreover, the response to SERM treatments (tamoxifen, endoxifen and toremifen) was investigated by cell viability and apoptosis measurements. An in silico analysis of survival data from the METABRIC study was performed in order to assess the prognostic value of miR-27a for response to SERM treatment.
Results:
Tamoxifen-resistant cells showed decreased expression of ERα and miR-27a. The overexpression of miR-27a increased the levels of ERα, while modulation of ERα decreased miR-27a expression. High miR-27a expression increased the sensitivity of MCF7 and T47D cells to SERM treatments and re-sensitized the cells to tamoxifen. Patient survival of luminal A breast cancer patients that underwent endocrine therapies was better in groups with high miR-27a expression.
Conclusion:
MiR-27a sensitizes luminal A breast cancer cells to SERM treatments based on a positive feedback loop with ERα. An increased overall-survival of ER-positive breast cancer patients that underwent endocrine treatments and displayed high miR-27a levels was found.
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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