Circ_0003998 upregulates ARK5 expression to elevate 5-Fluorouracil resistance in hepatocellular carcinoma through binding to miR-513a-5p.
Anticancer Drugs
; 33(10): 1103-1113, 2022 11 01.
Article
en En
| MEDLINE
| ID: mdl-36255069
ABSTRACT
Chemoresistance has limited clinical treatment of cancer patients. This study aimed to research the regulatory function of circ_0003998 in 5-Fluorouracil (5-FU) resistance. Circ_0003998, microRNA-513a-5p (miR-513a-5p) and AMPK-Related Protein Kinase 5 (ARK5) levels were assayed via the quantitative reverse transcription-PCR. Colony formation ability was assessed by colony formation assay. Flow cytometry was performed for cell cycle and cell apoptosis analysis. Caspase-3 activity was detected using a caspase-3 activity assay. Target analysis was conducted via RNA pull-down assay, a dual-luciferase reporter assay, and an RNA immunoprecipitation assay. In-vivo assay was performed by establishing a xenograft model in mice. Circ_0003998 was upregulated in 5-FU-resistant hepatocellular carcinoma (HCC) tissues and cells. Circ_0003998 downregulation repressed 5-FU resistance and cancer progression in 5-FU-resistant HCC cells. Circ_0003998 interacted with miR-513a-5p. Inhibition of miR-513a-5p reversed the regulation of sh-circ_0003998 in 5-FU resistance. ARK5 was a target of miR-513a-5p, and ARK5 was regulated by circ_0003998 via targeting miR-513a-5p. Circ_0003998 regulated 5-FU resistance partly by upregulating ARK5 expression. 5-FU sensitivity was enhanced after circ_0003998 level reduction in vivo. These findings unraveled that circ_0003998 elevated 5-FU resistance in HCC by sponging miR-513a-5p to upregulate the level of ARK5, indicating that circ_0003998 might be used as a target to improve 5-FU therapy for HCC.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
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Proteínas Represoras
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Carcinoma Hepatocelular
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MicroARNs
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Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Anticancer Drugs
Asunto de la revista:
ANTINEOPLASICOS
Año:
2022
Tipo del documento:
Article