JARID2 activation by NFYA promotes stemness of triple-negative breast cancer cells through the PI3K/AKT pathway.
Expert Rev Anticancer Ther
; 24(10): 1029-1040, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-39254227
ABSTRACT
BACKGROUND:
This study aimed to investigate the role of Jumonji AT Rich Interacting Domain 2 (JARID2) in regulating triple-negative breast cancer (TNBC) stemness and its mechanism. RESEARCH DESIGN ANDMETHODS:
Bioinformatics analysis examined JARID2 expression, prognosis, and transcription factors. Quantitative polymerase chain reaction, western blot, and immunohistochemistry detected expression. Dual luciferase reporter gene and chromatin immunoprecipitation assays verified binding. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay detected viability and proliferation. Sphere formation assay detected the sphere formation efficiency. Flow cytometry detected CD44+/CD24- -marked stem cells. A xenograft tumor model verified the effect of JARID2 in vivo.RESULTS:
JARID2 and nuclear transcription factor Y subunit α (NFYA) were upregulated in TNBC tissues and positively correlated. Knockdown of JARID2 or NFYA inhibited cell stemness by inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway. Enforced JARID2 expression rescued the suppressive effect of NFYA knockdown on the PI3K/AKT signaling pathway and cell stemness. Knockdown of JARID2 inhibited tumor growth and cell stemness in mice but was alleviated by concurrent overexpression of NFYA.CONCLUSIONS:
NFYA promotes TNBC cell stemness by upregulating JARID2 expression and regulating the PI3K/AKT signaling pathway, suggesting JARID2 as a potential target for innovating drugs that target TNBC stem cells.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
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Transducción de Señal
/
Proliferación Celular
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Proteínas Proto-Oncogénicas c-akt
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Neoplasias de la Mama Triple Negativas
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Expert Rev Anticancer Ther
Asunto de la revista:
NEOPLASIAS
/
TERAPEUTICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China