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Updated: Feb 16, 2026

Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System
Published on: April 23, 2021
miR-34a expression in human breast cancer is associated with drug resistance
Zhi-Hua Li1, Xueling Weng2, Qiu-Yun Xiong1
1Department of Breast Surgery, The Third Hospital of Nanchang City, Key Laboratory of Breast Diseases, Nanchang, Jiangxi 330009, P.R. China.
Abstract:
miR-34a is significantly down-regulated in breast cancer tissues and cell lines, which may be correlated with breast cancer multi-drug resistance (MDR). Here, we conducted cell-based experiments and clinical studies in a cohort of 113 breast cancer samples to analyze miR-34a expression and breast cancer MDR. Expression of miR-34a is down-regulated in the multi-drug resistant MDR-MCF-7 cells compared with its parental cells. Patients with miR-34a low expression had poorer overall survival (OS) and disease free survival (DFS) in comparison with those with high expression. Transfecting miR-34a mimics into MDR-MCF-7 breast cancer cells led to partial MDR reversal. Compared with the control group, miR-34a significantly reduced both the mRNA and protein expressions of BCL-2, CCND1 and NOTCH1, but no obvious changes were found in P53 or TOP-2a expression. In breast cancer tissue samples, the expression of miR-34a was related to BCL-2, CCND1 and NOTCH1, but not to HER-2, P53 and TOP-2a. Altogether, our findings suggest that miR-34a is an MDR and prognosis indicator of breast cancer, which may participate in the regulation of drug-resistant breast cancer by targeting BCL-2, CCND1, and NOTCH1.
Insights
MicroRNA-34a (miR-34a) down-regulation correlates with breast cancer multi-drug resistance (MDR). Restoring miR-34a expression can reverse MDR and improve patient prognosis by targeting BCL-2, CCND1, and NOTCH1.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-34a (miR-34a) is frequently downregulated in breast cancer.
- This downregulation may be linked to multi-drug resistance (MDR) in breast cancer.
- Understanding miR-34a's role is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the correlation between miR-34a expression and breast cancer MDR.
- To analyze the prognostic value of miR-34a in breast cancer patients.
- To identify the molecular targets of miR-34a involved in drug resistance.
Main Methods:
- Cell-based experiments using multi-drug resistant MCF-7 cells and their parental counterparts.
- Analysis of miR-34a expression in 113 breast cancer tissue samples.
- Quantitative assessment of mRNA and protein levels for target genes (BCL-2, CCND1, NOTCH1, P53, TOP-2a, HER-2).
Main Results:
- miR-34a expression was significantly lower in MDR-MCF-7 cells compared to parental cells.
- Low miR-34a expression in patients correlated with poorer overall survival (OS) and disease-free survival (DFS).
- miR-34a mimics partially reversed MDR and reduced BCL-2, CCND1, and NOTCH1 expression at mRNA and protein levels.
Conclusions:
- miR-34a acts as a potential biomarker for breast cancer MDR and prognosis.
- miR-34a may regulate drug resistance by targeting BCL-2, CCND1, and NOTCH1 in breast cancer.
- Further research into miR-34a could lead to novel therapeutic interventions for drug-resistant breast cancer.
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