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Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
Published on: February 20, 2017
Exploring Specific miRNA-mRNA Axes With Relationship to Taxanes-Resistance in Breast Cancer
Danni Chen1, Chang Bao2,3,4, Feng Zhao1
1Department of Radiation Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Abstract:
Breast cancer is the most prevalent type of malignancy in women worldwide. Taxanes (paclitaxel and docetaxel) are widely applied as first-line chemotherapeutic agents, while the therapeutic effect is seriously limited by the development of drug resistance. In the present study, we screened out several miRNAs dysregulated in taxanes-resistant breast cancer samples and confirmed that two miRNAs (miR-335-5p and let-7c-5p) played a major role in cell proliferation, apoptosis, and chemo-resistance. In addition, the weighted gene co-expression network analysis (WGCNA) for potential target genes of miR-335-5p and let-7c-5p identified three hub genes (CXCL9, CCR7, and SOCS1) with a positive relationship to taxanes-sensitivity. Further, target relationships between miR-335-5p and CXCL9, let-7c-5p and CCR7/SOCS1 were confirmed by dual-luciferase reporter assays. Importantly, the regulatory functions of CXCL9, CCR7, and SOCS1 on proliferation and chemoresistance were validated. In conclusion, our study shed light on clinical theragnostic relationships between miR-335-5p/CXCL9, let-7c-5p/CCR7/SOCS1 axes, and taxanes-resistance in breast cancer.
Insights
This study identifies two microRNAs (miRNAs) and three hub genes involved in taxane resistance in breast cancer. These findings offer potential theranostic targets to overcome chemoresistance and improve treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is the most common cancer in women globally.
- Taxanes are standard chemotherapy, but drug resistance limits efficacy.
- Understanding resistance mechanisms is crucial for improving breast cancer treatment.
Purpose of the Study:
- To identify microRNAs (miRNAs) and genes associated with taxane resistance in breast cancer.
- To elucidate the functional roles of identified miRNAs and genes in chemoresistance.
- To explore potential theranostic targets for overcoming taxane resistance.
Main Methods:
- Screening of dysregulated miRNAs in taxane-resistant breast cancer samples.
- Weighted Gene Co-expression Network Analysis (WGCNA) to identify hub genes.
- Dual-luciferase reporter assays to confirm miRNA-target interactions.
- Validation of gene functions in proliferation and chemoresistance.
Main Results:
- miR-335-5p and let-7c-5p were identified as key miRNAs in taxane resistance.
- CXCL9, CCR7, and SOCS1 were identified as hub genes positively related to taxane sensitivity.
- Direct regulatory relationships between miRNAs and hub genes were confirmed.
- CXCL9, CCR7, and SOCS1 were validated to regulate proliferation and chemoresistance.
Conclusions:
- The study highlights the theranostic potential of miR-335-5p/CXCL9 and let-7c-5p/CCR7/SOCS1 axes in taxane-resistant breast cancer.
- These molecular axes represent novel targets for overcoming chemotherapy resistance.
- Findings provide insights into the complex mechanisms underlying taxane resistance in breast cancer.
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