Methylation of neurofilament light polypeptide promoter is associated with cell invasion and metastasis in NSCLC.
Biochem Biophys Res Commun
; 470(3): 627-634, 2016 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-26801564
ABSTRACT
The role of NEFL in NSCLC remains largely unknown. Immunohistochemistry was performed to investigate the expression of NEFL in 108 lung cancer specimens. NEFL expression was associated with decreased lymph node metastases and favorable prognosis. Furthermore, real-time PCR and Western blot were used to investigate the expression of the NEFL gene in NSCLC cell lines. Subsequently, lentivirus-mediated RNA interference and overexpression were used to demonstrate that knocked-down of NEFL enhanced the invasion and migration of A549 and H460 NSCLC cells, whereas NEFL overexpression resulted in a suppression of the invasion and migration of GLC-82 and L78 cells in vitro. In addition, bisulfite sequence PCR assay demonstrated that NEFL downregulation was associated with promoter methylation, and NEFL expression was restored after treatment with 5-Aza-dC. Finally, we demonstrated that NEFL inhibited the NF-κB pathway, thereby suppressing the expression of uPA and decreasing NSCLC invasiveness and migration. Our studies suggest that NEFL methylation is a novel mechanism for NSCLC invasion and metastasis and that NEFL may represent a candidate biomarker for recurrence and survival in patients with NSCLC.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Regiões Promotoras Genéticas
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Proteínas de Neurofilamentos
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article