Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Mol Ther ; 32(4): 1110-1124, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38341612

RESUMO

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.


Assuntos
Carcinoma Hepatocelular , MicroRNAs , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Carcinoma Hepatocelular/patologia , Transdução de Sinais/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA