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Updated: Jan 24, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
circRNA_0025202 Regulates Tamoxifen Sensitivity and Tumor Progression via Regulating the miR-182-5p/FOXO3a Axis in
Yuting Sang1, Bing Chen2, Xiaojin Song1
1Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Abstract:
Tamoxifen is the most commonly used endocrine therapy for patients with hormone receptor (HR)-positive breast cancer. Despite its initial therapeutic efficacy, many patients eventually develop drug resistance, which remains a serious clinical challenge. To investigate roles of circular RNAs (circRNAs) in tamoxifen resistance, a tamoxifen-resistant MCF-7 cell line was established and screened for its circRNA expression profile by RNA sequencing. hsa_circ_0025202, a circRNA that was significantly downregulated, was selected for further investigation. Using a large cohort of clinical specimens, we found that hsa_circ_0025202 exhibited low expression in cancer tissues and was negatively correlated with lymphatic metastasis and histological grade. Gain- and loss-of-function assays indicated that hsa_circ_0025202 could inhibit cell proliferation, colony formation, and migration and increase cell apoptosis and sensitivity to tamoxifen. Bioinformatics and luciferase reporter assays verified that hsa_circ_0025202 could act as a miRNA sponge for miR-182-5p and further regulate the expression and activity of FOXO3a. Functional studies revealed that tumor inhibition and tamoxifen sensitization effects of hsa_circ_0025202 were achieved via the miR-182-5p/FOXO3a axis. Moreover, in vivo experiments confirmed that hsa_circ_0025202 could suppress tumor growth and enhance tamoxifen efficacy. Taken together, hsa_circ_0025202 served an anti-oncogenic role in HR-positive breast cancer, and it could be exploited as a novel marker for tamoxifen-resistant breast cancer.
Insights
Circular RNAs (circRNAs) like hsa_circ_0025202 show promise in overcoming tamoxifen resistance in hormone receptor-positive breast cancer by regulating the miR-182-5p/FOXO3a axis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hormone receptor (HR)-positive breast cancer is commonly treated with tamoxifen.
- Tamoxifen resistance is a significant clinical challenge, necessitating new therapeutic strategies.
- Circular RNAs (circRNAs) are emerging as key regulators in cancer development and drug resistance.
Purpose of the Study:
- To investigate the role of circRNAs in tamoxifen resistance in HR-positive breast cancer.
- To identify specific circRNAs involved in tamoxifen resistance.
- To elucidate the molecular mechanisms underlying the function of identified circRNAs.
Main Methods:
- Established a tamoxifen-resistant MCF-7 cell line and performed RNA sequencing to profile circRNA expression.
- Selected and validated the expression of hsa_circ_0025202 in clinical specimens.
- Conducted gain- and loss-of-function assays, bioinformatics analysis, luciferase reporter assays, and in vivo experiments.
Main Results:
- hsa_circ_0025202 was significantly downregulated in tamoxifen-resistant cells and associated with poorer prognostic factors.
- hsa_circ_0025202 suppressed cell proliferation, migration, and enhanced tamoxifen sensitivity.
- hsa_circ_0025202 acts as a miRNA sponge for miR-182-5p, regulating the miR-182-5p/FOXO3a axis.
Conclusions:
- hsa_circ_0025202 plays an anti-oncogenic role in HR-positive breast cancer.
- hsa_circ_0025202 can re-sensitize cells to tamoxifen by targeting the miR-182-5p/FOXO3a pathway.
- hsa_circ_0025202 holds potential as a novel therapeutic marker for tamoxifen-resistant breast cancer.
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