RNAi-mediated human Nestin silence inhibits proliferation and migration of malignant melanoma cells by G1/S arrest via Akt-GSK3ß-Rb pathway.
J Huazhong Univ Sci Technolog Med Sci
; 37(6): 895-903, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-29270750
ABSTRACT
Human Nestin (hNestin) has been found to express in melanoma, and its expression is positively correlated with the advanced stage of melanoma. However, the precise role of hNestin in the development of melanoma has not been fully understood. The present study aimed to explore the role of hNestin in the proliferation and invasion of melanoma cells. The lentivirus vector carrying a short hairpin RNAs (shRNAs) targeting hNestin (hNestin-shRNA-LV) was stably infected into human melanoma cells UACC903, which expressed high levels of hNestin. The effects of hNestin knockdown on the proliferation, apoptosis, migration of melanoma cells and the related signaling pathways were investigated by immunofluorence, Western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. The results showed that hNestin was expressed in most melanoma specimens and the melanoma cells studied. Knockdown of hNestin expression significantly inhibited the proliferation of melanoma cells, blocked the formation of cell colony, arrested cell cycle at G1/S stage and suppressed the activation of Akt and GSK3ß. hNestin-silent cells also showed a sheet-like appearance with tight cell-cell adhesion, decreased membrane expression of N-cadherin and ß-catenin, and attenuated migration. Furthermore, hNestin silence resulted in the inhibition of tumor growth in vivo. Our study indicates that hNestin knockdown suppresses the proliferation of melanoma cells, which might be through affecting Akt-GSK3ß-Rb pathway-mediated G1/S arrest, and hNestin silence inhibits the migration by selectively modulating the expression of cell adhesion molecules in the process of epithelial-mesenchymal transition.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Regulação Neoplásica da Expressão Gênica
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Proteína do Retinoblastoma
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Proteínas Proto-Oncogênicas c-akt
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Nestina
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Glicogênio Sintase Quinase 3 beta
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Melanoma
Idioma:
En
Revista:
J Huazhong Univ Sci Technolog Med Sci
Ano de publicação:
2017
Tipo de documento:
Article