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Updated: Feb 26, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
Penn Muluhngwi1, Negin Alizadeh-Rad1, Stephany L Vittitow1
1Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine University of Louisville, Louisville, KY, 40292, USA.
Abstract:
Aberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM resistance but acts as a tumor suppressor in TAM-resistant cells. The target genes mediating this tumor suppressor activity were unknown. Here, we identify miR-29b-1 and miR-29a target transcripts in both MCF-7 and LCC9 cells. We find that miR-29b-1 and miR-29a regulate common and unique transcripts in each cell line. The cell-specific and common downregulated genes were characterized using the MetaCore Gene Ontology (GO) enrichment analysis algorithm. LCC9-sepecific miR-29b-1/a-regulated GO processes include oxidative phosphorylation, ATP metabolism, and apoptosis. Extracellular flux analysis of cells transfected with anti- or pre- miR-29a confirmed that miR-29a inhibits mitochondrial bioenergetics in LCC9 cells. qPCR,luciferase reporter assays, and western blot also verified the ATP synthase subunit genes ATP5G1 and ATPIF1 as bone fide miR29b-1/a targets. Our results suggest that miR-29 repression of TAM-resistant breast cancer cell proliferation is mediated in part through repression of genes important in mitochondrial bioenergetics.
Insights
MicroRNA miR-29b-1/a acts as a tumor suppressor in tamoxifen-resistant breast cancer by inhibiting proliferation. It targets genes involved in mitochondrial bioenergetics, suggesting a novel therapeutic strategy for endocrine-resistant breast cancer.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Aberrant microRNA (miRNA) expression is implicated in breast cancer progression and endocrine resistance.
- Tamoxifen (TAM)-resistant breast cancer cells exhibit altered miRNA transcription, but the role of specific miRNAs like miR-29b-1/a in resistance is complex.
Purpose of the Study:
- To identify the target genes of miR-29b-1/a in both sensitive (MCF-7) and tamoxifen-resistant (LCC9) breast cancer cells.
- To elucidate the mechanism by which miR-29b-1/a suppresses proliferation in tamoxifen-resistant breast cancer cells.
Main Methods:
- Identification of miR-29b-1/a target transcripts using transcriptomic analysis.
- Gene Ontology (GO) enrichment analysis to characterize regulated processes.
- Extracellular flux analysis, quantitative PCR (qPCR), luciferase reporter assays, and Western blot to validate targets and mechanisms.
Main Results:
- miR-29b-1/a regulates distinct and overlapping sets of transcripts in MCF-7 and LCC9 cells.
- In LCC9 cells, miR-29b-1/a-regulated processes include oxidative phosphorylation, ATP metabolism, and apoptosis.
- ATP synthase subunit genes ATP5G1 and ATPIF1 were validated as direct targets of miR-29b-1/a, mediating the inhibition of mitochondrial bioenergetics and cell proliferation.
Conclusions:
- miR-29b-1/a functions as a tumor suppressor in tamoxifen-resistant breast cancer, independent of mediating resistance.
- The tumor-suppressive activity is partly achieved by repressing genes crucial for mitochondrial bioenergetics, such as ATP synthase subunits.
- Targeting miR-29b-1/a or its downstream effectors may offer a therapeutic avenue for endocrine-resistant breast cancer.
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