Related Experiment Video
Updated: Aug 14, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
MicroRNA Signatures of Fulvestrant-Treated Luminal Breast Cancer Cells: Identification of Therapeutic Targets
Ayako Nagata1, Yuya Tomioka2, Ryutaro Yasudome1
1Department of Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Abstract:
Estrogen receptor (ER)-positive breast cancer (BrCa) accounts for two-thirds of all BrCa cases worldwide. Therefore, ER-targeted endocrine therapy is the standard treatment for this disease. There has been a recent trend towards developing combination therapies using molecularly targeted drugs to improve outcomes. This study aimed to identify therapeutic targets demonstrating efficacy when combined with fulvestrant (a selective ER downregulator/degrader). We generated microRNA (miRNA) signatures from fulvestrant-treated MCF-7 cells by RNA sequencing. From the signature, we evaluated miR-374b-5p because its expression was elevated by fulvestrant treatment in MCF-7 cells. Also, in expression analysis by subtype of BrCa patients, miR-374b-5p expression was suppressed only in luminal BrCa. Ectopic expression assays revealed that miR-374b-5p attenuated the malignant phenotypes of MCF-7 cells. We searched for genes regulated by miR-374b-5p and discovered that 11 (NEK2, NUF2, HMMR, DEPDC1B, FOXM1, ELOVL6, KIF20A, NCAPH, CENPK, FAM83D, and KIAA0101) are closely involved in BrCa molecular pathogenesis. Among these target genes, we focused on forkhead box M1 (FOXM1), a transcription factor regulating cell cycle progression and division. Notably, combination therapy with fulvestrant and a FOXM1 inhibitor significantly suppressed MCF-7 cell proliferation. From the miRNA signature established in this study, we identified antitumor miR-374b-5p and its target genes and used these findings to explore candidate drugs with potential efficacy when combined with fulvestrant.
Insights
Researchers identified miR-374b-5p as a potential therapeutic target for estrogen receptor-positive breast cancer (BrCa). Combination therapy with fulvestrant and a FOXM1 inhibitor showed significant suppression of BrCa cell proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Estrogen receptor (ER)-positive breast cancer (BrCa) is the most common subtype worldwide.
- Endocrine therapy targeting ER is the standard treatment for ER-positive BrCa.
- Combination therapies with targeted drugs are emerging to improve treatment outcomes.
Purpose of the Study:
- To identify novel therapeutic targets for combination therapy with fulvestrant, a selective ER downregulator.
- To investigate the role of microRNA (miRNA) signatures in response to fulvestrant treatment.
- To evaluate miR-374b-5p and its downstream targets as potential therapeutic strategies for BrCa.
Main Methods:
- RNA sequencing was used to generate miRNA signatures from fulvestrant-treated MCF-7 cells.
- Expression analysis of miR-374b-5p in BrCa subtypes.
- Ectopic expression assays and target gene identification for miR-374b-5p.
- Combination therapy studies using fulvestrant and a FOXM1 inhibitor in MCF-7 cells.
Main Results:
- Fulvestrant treatment elevated miR-374b-5p expression in MCF-7 cells.
- miR-374b-5p expression was suppressed in luminal BrCa subtypes.
- Ectopic expression of miR-374b-5p attenuated malignant phenotypes of MCF-7 cells.
- FOXM1 was identified as a key target gene of miR-374b-5p involved in BrCa pathogenesis.
- Combination therapy with fulvestrant and a FOXM1 inhibitor significantly suppressed MCF-7 cell proliferation.
Conclusions:
- miR-374b-5p acts as an antitumor miRNA in ER-positive breast cancer.
- FOXM1 is a critical therapeutic target for combination therapy with fulvestrant.
- This study identifies novel therapeutic strategies for ER-positive BrCa by targeting miR-374b-5p and its downstream genes.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs