Pseudohypoxia induced by miR-126 deactivation promotes migration and therapeutic resistance in renal cell carcinoma.
Cancer Lett
; 394: 65-75, 2017 05 28.
Article
en En
| MEDLINE
| ID: mdl-28257806
Pseudohypoxia plays a central role in the progression and therapeutic resistance of clear cell renal cell carcinoma (ccRCC); however, the underlying mechanisms are poorly understood. MicroRNA miR-126 has decreased expression in metastatic or relapsed ccRCC as compared to primary tumors, but the mechanisms by which miR-126 is implicated in RCC remain unknown. Through RNA-seq profiling to evaluate the impact of overexpression or CRISPR knockout of miR-126, we have identified SERPINE1 as a miR-126-5p target regulating cell motility, and SLC7A5 as a miR-126-3p target regulating the mTOR/HIF pathway. Specifically, miR-126 inhibits HIFα protein expression independent of von Hippel-Lindau tumor suppressor (VHL). On the other hand, deactivation of miR-126 induces a pseudohypoxia state due to increased HIFα expression, which further enhances therapeutic resistance and cell motility mediated by SLC7A5 and SERPINE1, respectively. Finally, the clinical relevance of miR-126 modulated gene regulation in ccRCC has been confirmed with profiling data from The Cancer Genome Atlas.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tolerancia a Radiación
/
Carcinoma de Células Renales
/
Movimiento Celular
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Cisplatino
/
Resistencia a Antineoplásicos
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MicroARNs
/
Hipoxia Tumoral
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Neoplasias Renales
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cancer Lett
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Irlanda