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Aging (Albany NY) ; 13(2): 2604-2625, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33428600

RESUMO

Many studies have reported that estrogen (E2) promotes lung cancer by binding to nuclear estrogen receptors (ER), and altering ER related nuclear protein expressions. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in lung adenocarcinoma (LUAD), and the co-expression of CENPF and ERß was found in the nucleus of LUAD cells through immunofluorescence. We identified the nuclear protein CENPF and explored its relationship with the ER pathway. CENPF and ERß2/5 were related with T stage and poor prognosis (P<0.05). CENPF knockout significantly inhibited LUAD cell growth, the tumor growth of mice and the expression of ERß2/5 (P<0.05). The protein expression of CENPF and ERß2/5 in the CENPF-Knockdown+Fulvestrant group was lower than CENPF- Negative Control +Fulvestrant group (P=0.002, 0.004, 0.001) in A549 cells. The tumor size and weight of the CENPF-Knockdown+Fulvestrant group were significantly lower than CENPF- Negative Control +Fulvestrant group (P=0.001, 0.039) in nude mice. All the results indicated that both CENPF and ERß2/5 play important roles in the progression of LUAD, and knockdown CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERß2/5 and CENPF remained more effective in improving the therapeutic effect of LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Proteínas Cromossômicas não Histona/genética , Receptor beta de Estrogênio/metabolismo , Neoplasias Pulmonares/genética , Proteínas dos Microfilamentos/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Proteínas Cromossômicas não Histona/metabolismo , Biologia Computacional , Bases de Dados Factuais , Progressão da Doença , Antagonistas do Receptor de Estrogênio/farmacologia , Fulvestranto/farmacologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Proteínas dos Microfilamentos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
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