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Métodos Terapêuticos e Terapias MTCI
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1.
Int J Biochem Cell Biol ; 94: 107-118, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29175387

RESUMO

Baicalein, an active flavonoid extracted from the root of Scutellaria baicalensis Georgi, has fascinating anti-cancer effects on many cancers. Our previous study also found that baicalein inhibited cervical cancer cell proliferation and migration, and induced cervical cancer cell apoptosis and cell cycle arrest. However, the molecular mechanisms underlying the anti-cancer effects of baicalein are largely unknown. In this study, we identified a novel long noncoding RNA (lncRNA), which is downregulated by baicalein in a dose- and time-dependent manner in cervical cancer. We named this lncRNA as baicalein down-regulated long noncoding RNA (BDLNR). Gain-of- and loss-of-function assays showed that BDLNR was required for baicalein-induced cell proliferation inhibition, cell death induction, migration inhibition, and in vivo tumor growth inhibition of cervical cancer. Mechanistically, BDLNR physically bound to YBX1, recruited YBX1 to PIK3CA promoter, activated PIK3CA expression and PI3K/Akt pathway. Furthermore, BDLNR was upregulated in cervical cancer and associated with poor prognosis of cervical cancer patients. Collectively, our data demonstrated that BDLNR mediated the anti-cancer effects of baicalein in cervical cancer via activating PI3K/Akt pathway, and implied that BDLNR would be potential therapeutic target for enhancing the anti-cancer effects of baicalein in cervical cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Colo do Útero/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Flavanonas/uso terapêutico , RNA Longo não Codificante/antagonistas & inibidores , RNA Neoplásico/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Colo do Útero/metabolismo , Colo do Útero/patologia , Feminino , Flavanonas/efeitos adversos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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