Histone deacetylase 9 downregulation decreases tumor growth and promotes apoptosis in non-small cell lung cancer after melatonin treatment.
J Pineal Res
; 67(2): e12587, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31090223
ABSTRACT
Histone deacetylase 9 functions as an oncogene in a variety of cancers, but its role on non-small cell lung cancer (NSCLC) has not been reported. Melatonin was proven to possess anticancer actions, whereas its effect on NSCLC and underlying mechanisms remains poorly understood. In this study, 337 patients with complete clinicopathologic characteristics who underwent NSCLC surgery were recruited for the study. We found that NSCLC patients with high HDAC9 expression were correlated with worse overall survival and poor prognosis. HDAC9 knockdown significantly reduced NSCLC cell growth and induced apoptosis both in vivo and in vitro. Melatonin application also markedly inhibited cell proliferation, metastasis, and invasion and promoted apoptosis in NSCLC cells. Moreover, RNA-seq, real-time quantitative polymerase chain reaction, and western blot analyses showed that melatonin treatment decreased the HDAC9 level in NSCLC cells. A mechanistic study revealed that HDAC9 knockdown further enhanced the anticancer activities of melatonin treatment, whereas HDAC9 overexpression partially reversed the melatonin's anticancer effects. Additionally, the in vivo study found melatonin exerted anti-proliferative and pro-apoptotic effects on xenograft tumors which were also strengthened by HDAC9 knockdown. These results indicated that HDAC9 downregulation mediated the anti-NSCLC actions of melatonin, and targeting HDAC9 may be the novel therapeutic strategy for NSCLC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Regulação para Baixo
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Regulação Enzimológica da Expressão Gênica
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Regulação Neoplásica da Expressão Gênica
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Apoptose
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Carcinoma Pulmonar de Células não Pequenas
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Histona Desacetilases
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Neoplasias Pulmonares
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Melatonina
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article