Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer.
Exp Mol Med
; 50(9): 1-14, 2018 09 12.
Article
en En
| MEDLINE
| ID: mdl-30209296
ß-Elemene, an active component of natural plants, has been shown to exhibit anticancer properties. However, the detailed mechanism underlying these effects has yet to be determined. In this study, we show that ß-elemene inhibits the growth of lung cancer cells. Mechanistically, we found that ß-elemene decreased the phosphorylation of signal transducer and activator of transcription 3 (Stat3) and miRNA155-5p mRNA but induced the protein expression of human forkhead box class O (FOXO)3a; the latter two were abrogated in cells with overexpressed Stat3. Notably, miRNA155-5p mimics reduced FOXO3a luciferase reporter activity in the 3-UTR region and protein expression, whereas overexpressed FOXO3a countered the reduction of the miRNA155-5p levels by ß-elemene. Moreover, ß-elemene increased the mRNA and protein expression levels as well as promoter activity of insulin-like growth factor-binding protein 1 (IGFBP1); this finding was not observed in cells with a silenced FOXO3a gene and miRNA155-5p mimics. Finally, silencing of IGFBP1 blocked ß-elemene-inhibited cell growth. Similar findings were observed in vivo. In summary, our results indicate that ß-elemene increases IGFBP1 gene expression via inactivation of Stat3 followed by a reciprocal interaction between miRNA155-5p and FOXO3a. This effect leads to inhibition of human lung cancer cell growth. These findings reveal a novel molecular mechanism underlying the inhibitory effects of ß-elemene on lung cancer cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sesquiterpenos
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Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina
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MicroARNs
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Factor de Transcripción STAT3
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Proteína Forkhead Box O3
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Exp Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos