PGC-1α/SNAI1 axis regulates tumor growth and metastasis by targeting miR-128b in gastric cancer.
J Cell Physiol
; 234(10): 17232-17241, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30684287
ABSTRACT
Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator that has been characterized as master regulators of mitochondrial biogenesis. It has been reported that aberrant regulation of PGC-1α is involved in a variety of human cancers. However, whether PGC-1α is involved in the regulation of tumor growth and metastasis in gastric cancer (GC) remains unknown. In the present study, we found that the expression of PGC-1α was upregulated in GC tissues and GC cell lines. Inhibition of PGC-1α inhibited cell viability, migration, and invasion, and promoted cell apoptosis of GC cells. Furthermore, inhibition of PGC-1α downregulated the SNAI1 expression, whereas upregulated microRNA (miR)-128b expression. The expression of SNAI1 was upregulated and the expression of miR-128b was downregulated in GC tissues. We further found that there was a positive correlation between PGC-1α and SNAI1 expression, and a negative correlation between PGC-1α and miR-128b expression or between SNAI1 and miR-128b expression in GC tissues. Moreover, PGC-1α inhibition-induced increased miR-128b expression, and PGC-1α overexpression-induced decreased miR-128b expression were both markedly suppressed by SNAI1 overexpression. In addition, SNAI1 overexpression or miR-128b inhibition partly reversed the effects of PGC-1α inhibition in GC cells. Furthermore, inhibition of PGC-1α suppressed the tumor growth in a nude mouse model, which may be related with the dysregulation of SNAI1 and miR-128b. In conclusion, these data indicate that the PGC-1α/SNAI1/miR-128b axis plays a vital role in GC via regulating cell viability, migration, invasion, and apoptosis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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MicroRNAs
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Fatores de Transcrição da Família Snail
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article