التفاصيل البيبلوغرافية
| العنوان: |
Role of neurofilament light polypeptide in head and neck cancer chemoresistance |
| المؤلفون: |
Kevin J. Cullen, Baishen Chen, Zhongmin Guo, Kenneth P. Nephew, Michael G. House, Ju Chen |
| المصدر: |
Molecular cancer research : MCR. 10(3) |
| سنة النشر: |
2012 |
| مصطلحات موضوعية: |
Male, Cancer Research, Down-Regulation, Biology, Tuberous Sclerosis Complex 1 Protein, Downregulation and upregulation, Neurofilament Proteins, Cell Line, Tumor, medicine, Humans, Gene Silencing, RNA, Messenger, Promoter Regions, Genetic, Molecular Biology, PI3K/AKT/mTOR pathway, Cisplatin, Gene knockdown, TOR Serine-Threonine Kinases, Tumor Suppressor Proteins, Cancer, DNA Methylation, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Gene Expression Regulation, Neoplastic, Neurofilament Light Polypeptide, medicine.anatomical_structure, Oncology, Drug Resistance, Neoplasm, Head and Neck Neoplasms, DNA methylation, Cancer research, Female, TSC1, Peptides, medicine.drug, Protein Binding, Signal Transduction |
| الوصف: |
Resistance to cisplatin-based chemotherapy is responsible for therapeutic failure of many common human cancers including cancer of head and neck (HNC). Mechanisms underlying cisplatin resistance remain unclear. In this study, we identified neurofilament light polypeptide (NEFL) as a novel hypermethylated gene associated with resistance to cisplatin-based chemotherapy in HNC. Analysis of 14 HNC cell lines revealed that downregulation of NEFL expression significantly correlated with increased resistance to cisplatin. Hypermethylation of NEFL promoter CpG islands was observed in cell lines as examined by bisulfite DNA sequencing and methylation-specific PCR (MSP) and tightly correlated with reduced NEFL mRNA and protein expression. Furthermore, in patient samples with HNC (n = 51) analyzed by quantitative MSP, NEFL promoter hypermethylation was associated with resistance to cisplatin-based chemotherapy [relative risk (RR), 3.045; 95% confidence interval (CI), 1.459–6.355; P = 0.007] and predicted diminished overall and disease-free survival for patients treated with cisplatin-based chemotherapy. Knockdown of NEFL by siRNA in the highly cisplatin-sensitive cell line PCI13 increased (P < 0.01) resistance to cisplatin. In cisplatin-resistant O11 and SCC25cp cells, restored expression of NEFL significantly increased sensitivity to the drug. Furthermore, NEFL physically associated with tuberous sclerosis complex 1 (TSC1), a known inhibitor of the mTOR pathway, and NEFL downregulation led to functional activation of mTOR pathway and consequentially conferred cisplatin resistance. This is the first study to show a role for NEFL in HNC chemoresistance. Our findings suggest that NEFL methylation is a novel mechanism for HNC chemoresistance and may represent a candidate biomarker predictive of chemotherapeutic response and survival in patients with HNC. Mol Cancer Res; 10(3); 305–15. ©2012 AACR. |
| تدمد: |
1557-3125 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b554121daa7fbc00b83d1040292f7318
https://pubmed.ncbi.nlm.nih.gov/22246235 |
| رقم الانضمام: |
edsair.doi.dedup.....b554121daa7fbc00b83d1040292f7318 |
| قاعدة البيانات: |
OpenAIRE |