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Published on: September 8, 2017
MicroRNA expression profiles of head and neck squamous cell carcinoma with docetaxel-induced multidrug resistance
Yuemeng Dai1, Cheng-Hui Xie, John P Neis
1Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Background:
The purpose of this study was to investigate the potential role of variable microRNA (miRNA) expression in the development of multidrug resistance (MDR) in head and neck cancer.
Methods:
Head and neck squamous cell carcinoma cell lines UMSCC-1 and SQ20B were treated with docetaxel at increasing concentrations to develop resistant cell lines. Parental and resistant cells were treated with cisplatin, 5-fluorouracil, paclitaxel, methotrexate, and doxorubicin to confirm cross-resistance. The miRNA pattern of resistant cells was then compared with their parental cells.
Results:
Docetaxel treatment successfully induced resistance primarily and induced multidrug cross-resistance. Resistant cells showed significant downregulation of miR-100, miR-130a, and miR-197 and upregulation in miR-101, miR-181b, miR-181d, and miR-195 expression when compared with their parent cells (p < .01). Real-time polymerase chain reaction (PCR) analysis confirmed statistically significant downregulation in miR-100 and miR-130a and upregulation in miR-181d expression (p < .001).
Conclusion:
Alterations in miRNA expression has direct relationship to MDR in head and neck cancer and may serve as biomolecular targets for reversal of MDR.
Insights
Variable microRNA (miRNA) expression is linked to multidrug resistance (MDR) in head and neck cancer. Specific miRNA changes may offer new therapeutic targets for overcoming MDR in these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Head and neck cancer frequently develops multidrug resistance (MDR).
- The role of microRNA (miRNA) in MDR development is not fully understood.
- Investigating miRNA expression patterns can reveal mechanisms of MDR.
Purpose of the Study:
- To explore the association between variable miRNA expression and MDR in head and neck cancer.
- To identify specific miRNAs that are altered in drug-resistant head and neck cancer cells.
- To assess the potential of miRNAs as therapeutic targets for MDR reversal.
Main Methods:
- Established docetaxel-resistant head and neck squamous cell carcinoma (HNSCC) cell lines (UMSCC-1, SQ20B).
- Confirmed cross-resistance to various chemotherapeutic agents (cisplatin, 5-fluorouracil, paclitaxel, methotrexate, doxorubicin).
- Compared miRNA expression profiles between parental and resistant HNSCC cells using molecular techniques.
Main Results:
- Docetaxel treatment successfully induced MDR and cross-resistance in HNSCC cell lines.
- Significant downregulation of miR-100, miR-130a, and miR-197 observed in resistant cells.
- Significant upregulation of miR-101, miR-181b, miR-181d, and miR-195 noted in resistant cells (p < .01).
- Real-time PCR confirmed downregulation of miR-100, miR-130a and upregulation of miR-181d (p < .001).
Conclusions:
- Altered miRNA expression is directly correlated with MDR in head and neck cancer.
- Specific miRNAs (e.g., miR-100, miR-130a, miR-181d) are key players in MDR development.
- These altered miRNAs represent potential diagnostic biomarkers and therapeutic targets for reversing MDR in head and neck cancer.
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