Related Experiment Video
Updated: Apr 19, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
MicroRNA-574-3p, identified by microRNA library-based functional screening, modulates tamoxifen response in breast
T Ujihira1, K Ikeda2, T Suzuki3
11] Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan [2] Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.
Abstract:
Most primary breast cancers express estrogen receptor α and can be treated via endocrine therapy using anti-estrogens such as tamoxifen; however, acquired endocrine resistance is a critical issue. To identify tamoxifen response-related microRNAs (miRNAs) in breast cancer, MCF-7 cells infected with a lentiviral miRNA library were treated with 4-hydroxytamoxifen (OHT) or vehicle for 4 weeks, and the amounts of individual miRNA precursors that had integrated into the genome were evaluated by microarray. Compared to the vehicle-treated cells, 5 'dropout' miRNAs, which were downregulated in OHT-treated cells, and 6 'retained' miRNAs, which were upregulated in OHT-treated cells, were identified. Of the dropout miRNAs, we found that miR-574-3p expression was downregulated in clinical breast cancer tissues as compared with their paired adjacent tissues. In addition, anti-miR-574-3p reversed tamoxifen-mediated suppression of MCF-7 cell growth. Clathrin heavy chain (CLTC) was identified as a miR-574-3p target gene by in silico algorithms and luciferase reporter assay using the 3' untranslated region of CLTC mRNA. Interestingly, loss and gain of miR-574-3p function in MCF-7 cells causes CLTC to be upregulated and downregulated, respectively. These results suggest that functional screening mediated by miRNA libraries can provide new insights into the genes essential for tamoxifen response in breast cancer.
Insights
This study identified microRNAs (miRNAs) involved in tamoxifen response in breast cancer. Downregulation of miR-574-3p was linked to tamoxifen resistance, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Estrogen receptor α (ERα) is a key target in breast cancer therapy.
- Tamoxifen resistance is a significant clinical challenge in ERα-positive breast cancer.
- MicroRNAs (miRNAs) play crucial roles in gene regulation and cancer progression.
Purpose of the Study:
- To identify microRNAs (miRNAs) associated with tamoxifen response in breast cancer.
- To investigate the role of specific miRNAs in acquired endocrine resistance.
- To explore potential miRNA-based therapeutic strategies for tamoxifen-resistant breast cancer.
Main Methods:
- Functional screening of a lentiviral miRNA library in MCF-7 breast cancer cells treated with 4-hydroxytamoxifen (OHT).
- Microarray analysis to quantify miRNA precursor integration and identify differentially expressed miRNAs.
- In silico analysis and luciferase reporter assays to validate miRNA-target interactions.
Main Results:
- Five 'dropout' miRNAs (downregulated) and six 'retained' miRNAs (upregulated) were identified in response to OHT treatment.
- miR-574-3p was found to be downregulated in clinical breast cancer tissues and its inhibition reversed tamoxifen-mediated growth suppression.
- Clathrin heavy chain (CLTC) was validated as a direct target of miR-574-3p, with inverse expression patterns.
Conclusions:
- Functional miRNA screening is effective for discovering genes involved in tamoxifen response.
- miR-574-3p downregulation contributes to tamoxifen resistance in breast cancer by upregulating CLTC.
- Targeting miR-574-3p or its downstream effectors may offer novel therapeutic avenues for endocrine-resistant breast cancer.
Related Concept Videos
MicroRNAs
MicroRNAs
MicroRNAs
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
mTOR Signaling and Cancer Progression
The mTOR pathway or the...

