TGF-ß-SMAD-miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop.
Carcinogenesis
; 40(5): 695-705, 2019 07 04.
Article
en En
| MEDLINE
| ID: mdl-30475986
Transforming growth factor-ß (TGF-ß) pathway plays crucial roles during the carcinogenesis and metastasis. TGF-ß receptor 2 (TGFBR2) is a key molecule for the regulation of TGF-ß pathway and frequently downregulated or lost in several cancer types including non-small cell lung cancer (NSCLC), and TGF-ß pathway is often regulated by negative-feedback mechanisms, but little is known about the mechanism of TGFBR2 downregulation in NSCLC. Here, we found that the expression of miR-520e is upregulated in metastatic tumor tissues compared with non-metastatic ones, and its expression is inversely correlated with that of TGFBR2 in clinical samples. We also discovered that TGF-ß dramatically increased the expression of miR-520e, which targeted and downregulated TGFBR2, and the suppression of miR-520e significantly impaired TGF-ß-induced TGFBR2 downregulation. Chromatin immunoprecipitation-PCR experiments further showed that miR-520e is transcriptionally induced by SMAD2/3 in response to TGF-ß. Our findings reveal a novel negative-feedback mechanism in TGF-ß signaling and the expression level of miR-520e could be a predictive biomarker for NSCLC metastasis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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MicroARNs
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Proteína Smad2
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Proteína smad3
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Factor de Crecimiento Transformador beta1
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Receptor Tipo II de Factor de Crecimiento Transformador beta
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Carcinogenesis
Año:
2019
Tipo del documento:
Article
País de afiliación:
Turquía