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FEBS Lett ; 594(19): 3108-3121, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32671843

RESUMO

Apolipoprotein L1 (APOL1) participates in lipid metabolism. Here, we investigate the mechanisms regulating APOL1 gene expression in hepatoma cells. We demonstrate that the -80-nt to +31-nt region of the APOL1 promoter, which contains one SP transcription factor binding GT box and an interferon regulatory factor (IRF) binding ISRE element, maintains the maximum activity. Mutation of the GT box and ISRE element dramatically reduces APOL1 promoter activity. EMSA and chromatin immunoprecipitation assay reveal that the transcription factors Sp1, IRF1 and IRF2 could interact with their cognate binding sites on the APOL1 promoter. Overexpression of Sp1, IRF1 and IRF2 increases promoter activity, leading to increased APOL1 mRNA and protein levels, while knockdown of Sp1, IRF1 and IRF2 has the opposite effects. These results demonstrate that the APOL1 gene could be regulated by Sp1, IRF1 and IRF2 in hepatoma cells.


Assuntos
Apolipoproteína L1/genética , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Fator Regulador 1 de Interferon/metabolismo , Fator Regulador 2 de Interferon/metabolismo , Neoplasias Hepáticas/genética , Fator de Transcrição Sp1/metabolismo , Transcrição Gênica , Apolipoproteína L1/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Células HEK293 , Humanos , Regiões Promotoras Genéticas , Ligação Proteica , Elementos de Resposta/genética
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