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Cancer Sci ; 115(8): 2659-2672, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38710213

RESUMO

Circular RNAs (circRNAs) have emerged as crucial regulators in tumor progression, yet their specific role in hepatocellular carcinoma (HCC) remains largely uncharacterized. In this study, we utilized high-transcriptome sequencing to identify the upregulation of circESYT2 (hsa_circ_002142) in HCC tissues. Functional experiments carried out in vivo and in vitro revealed that circESYT2 played a significant role in maintaining the growth and metastatic behaviors of HCC. Through integrative analysis, we identified enolase 2 (ENO2) as a potential target regulated by circESYT2 through the competitive endogenous RNA sponge mechanism. Additional gain- or loss-of-function experiments indicated that overexpression of circESYT2 led to a tumor-promoting effect, which could be reversed by transfection of microRNA-665 (miR-665) mimic or ENO2 knockdown in HCC cells. Furthermore, the direct interaction between miR-665 and circESYT2 and between miR-665 and ENO2 was confirmed using RNA immunoprecipitation, FISH, RNA pull-down, and dual-luciferase reporter assays, highlighting the involvement of the circESYT2/miR-665/ENO2 axis in promoting HCC progression. These findings shed light on the molecular characteristics of circESYT2 in HCC tissues and suggest its potential as a biomarker or therapeutic target for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , Fosfopiruvato Hidratase , RNA Circular , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Humanos , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , MicroRNAs/genética , RNA Circular/genética , Animais , Camundongos , Linhagem Celular Tumoral , Masculino , Feminino , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proliferação de Células/genética , Pessoa de Meia-Idade , Camundongos Nus , Regulação para Cima/genética
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