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Updated: Jan 29, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Expression pattern of microRNAs related with response to trastuzumab in breast cancer
Fan Yang1,2, Ziyi Fu1,3, Mengzhu Yang1,2
1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background:
Although an immense effort has been made to develop a novel biomarker for response to trastuzumab, no reliable biomarkers are available to guide management, expect for HER2. The aim of this study was to examine the relationship between microRNA (miRNA) expression and resistance to trastuzumab.
Methods:
Differentially expressed miRNAs between trastuzumab-resistant and trastuzumab-sensitive cell lines were analyzed using microarrays. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to determine the functions of differentially expressed miRNA and their targeted genes. Furthermore, the protein-protein interactions (PPI) network was analyzed. Serum samples were collected from patients with HER2-positive breast cancer who were treated with trastuzumab. We validated the miRNAs expression levels by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in these serums. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the miRNA.
Results:
Using miRNA microarrays, 151 miRNAs that significant differentially expressed between the trastuzumab-resistant and sensitive cells were identified, including 46 upregulated and 105 downregulated miRNAs. Results of real-time PCR confirmed seven miRNAs in cell lines. PI3K-Akt signaling pathway was involved in regulating biological function according to KEGG analysis. Compared with the serums of trastuzumab-sensitive patients, three miRNAs, namely miR-200b, miR-135b, and miR-29a, were identified to be upregulated, and miR-224 was downregulated in the trastuzumab-resistant serums. ROC analysis showed that four miRNAs were correlated with trastuzumab resistance. Furthermore, three subnetwork modules of PPI network were obtained.
Conclusion:
The results indicated that miRNAs were reliable predictive biomarkers for response to trastuzumab.
Insights
MicroRNAs (miRNAs) show promise as predictive biomarkers for trastuzumab response in HER2-positive breast cancer. This study identified specific miRNA expression patterns in resistant versus sensitive cell lines and patient serums, suggesting their potential in guiding treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Trastuzumab is a key therapy for HER2-positive breast cancer, but reliable biomarkers predicting response are lacking beyond HER2 status.
- Identifying novel biomarkers is crucial for optimizing trastuzumab treatment strategies.
Purpose of the Study:
- To investigate the association between microRNA (miRNA) expression profiles and trastuzumab resistance in HER2-positive breast cancer.
- To identify potential miRNA biomarkers for predicting patient response to trastuzumab therapy.
Main Methods:
- Microarray analysis identified differentially expressed miRNAs in trastuzumab-resistant versus sensitive cell lines.
- Gene Ontology and KEGG pathway analyses elucidated the functions of identified miRNAs and their targets.
- Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and receiver operating characteristic (ROC) curve analysis were used for validation and predictive performance evaluation in patient serum samples.
Main Results:
- 151 differentially expressed miRNAs were identified between resistant and sensitive cell lines.
- KEGG analysis implicated the PI3K-Akt signaling pathway.
- Four miRNAs (miR-200b, miR-135b, miR-29a, and miR-224) showed significant correlation with trastuzumab resistance in patient serums.
Conclusions:
- MicroRNAs demonstrate potential as reliable predictive biomarkers for trastuzumab response.
- These findings may aid in personalizing trastuzumab treatment for HER2-positive breast cancer patients.
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