MicroRNA-431-5p inhibits angiogenesis, lymphangiogenesis, and lymph node metastasis by affecting TGF-ß1/SMAD2/3 signaling via ZEB1 in gastric cancer.
Mol Carcinog
; 63(7): 1378-1391, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38656643
ABSTRACT
Accumulating evidence suggests that lymphangiogenesis plays a crucial role in lymphatic metastasis, leading to tumor immune tolerance. However, the specific mechanism remains unclear. In this study, miR-431-5p was markedly downregulated in both gastric cancer (GC) tissues and plasma exosomes, and its expression were correlated negatively with LN metastasis and poor prognosis. Mechanistically, miR-431-5p weakens the TGF-ß1/SMAD2/3 signaling pathway by targeting ZEB1, thereby suppressing the secretion of VEGF-A and ANG2, which in turn hinders angiogenesis, lymphangiogenesis, and lymph node (LN) metastasis in GC. Experiments using a popliteal LN metastasis model in BALB/c nude mice demonstrated that miR-431-5p significantly reduced popliteal LN metastasis. Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-ß1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Gástricas
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Transducción de Señal
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Regulación Neoplásica de la Expresión Génica
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MicroARNs
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Linfangiogénesis
/
Proteína Smad2
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Proteína smad3
/
Factor de Crecimiento Transformador beta1
/
Homeobox 1 de Unión a la E-Box con Dedos de Zinc
/
Metástasis Linfática
Límite:
Animals
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
China