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Published on: February 24, 2026
MiR-654-5p attenuates breast cancer progression by targeting EPSTI1
Yu-Yan Tan1, Xiao-Yun Xu2, Jin-Feng Wang3
1Department of General Surgery, The First College of Clinical Medical Science, China Three Gorges UniversityYichang 443003, Hubei, China; Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast UniversityNanjing 210009, Jiangsu, China.
Abstract:
MicroRNAs (miRNAs) dysregulation is a common event in a variety of human diseases including breast cancer. However, clinical relevance and biological role of miR-654-5p in the progression of breast cancer remain greatly elusive. Herein, the expression levels of miR-654-5p were aberrantly downregulated in human breast cancer specimens and four breast cancer cell lines. Low expression of miR-654-5p was strongly associated with advanced TNM stage and lymph node metastasis as well as a poor survival. Functional analysis showed that miR-654-5p overexpression inhibited cell growth and invasion, and induced cell apoptosis in two aggressive breast cancer cells. Further studies demonstrated that Epithelial stromal interaction 1 (EPSTI1) was a direct target gene of miR-654-5p and showed an inverse correlation with miR-654-5p expression. Forced expression of EPSTI1 could abrogate the inhibitory effect of miR-654-5p on the growth and invasion of breast cancer cells as well as apoptosis-induced ability. In conclusion, the present study highlights that miR-654-5p acts as a tumor suppressor in breast cancer through directly targeting EPSTI1, and their functional regulation may open a novel avenue with regard to the therapeutic target for breast cancer.
Insights
MicroRNA-654-5p (miR-654-5p) is downregulated in breast cancer, suppressing tumor growth and invasion by targeting EPSTI1. Restoring miR-654-5p offers a potential therapeutic strategy for breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) dysregulation is implicated in various human diseases, including breast cancer.
- The specific role and clinical significance of miR-654-5p in breast cancer progression are not well understood.
Purpose of the Study:
- To investigate the expression levels, clinical relevance, and biological function of miR-654-5p in breast cancer.
- To identify the direct target of miR-654-5p and elucidate its mechanism in breast cancer progression.
Main Methods:
- Quantitative real-time PCR to assess miR-654-5p expression in breast cancer tissues and cell lines.
- Functional assays including cell growth, invasion, and apoptosis assays upon miR-654-5p overexpression.
- Luciferase reporter assays and Western blotting to validate EPSTI1 as a direct target of miR-654-5p.
Main Results:
- miR-654-5p was significantly downregulated in breast cancer specimens and cell lines.
- Low miR-654-5p expression correlated with advanced TNM stage, lymph node metastasis, and poor patient survival.
- Overexpression of miR-654-5p inhibited breast cancer cell growth and invasion while promoting apoptosis.
- EPSTI1 was identified as a direct target of miR-654-5p, with inverse expression correlation.
- EPSTI1 overexpression reversed the tumor-suppressive effects of miR-654-5p.
Conclusions:
- miR-654-5p functions as a tumor suppressor in breast cancer by directly targeting EPSTI1.
- The miR-654-5p/EPSTI1 axis represents a potential novel therapeutic target for breast cancer treatment.
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