Oncogenic circular RNA Hsa-circ-000684 interacts with microRNA-186 to upregulate ZEB1 in gastric cancer.
FASEB J
; 34(6): 8187-8203, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32388910
ABSTRACT
Circular RNAs (circRNAs) function as modulators of microRNAs (miRNAs) and are often involved in cancer progression. This study aims to investigate the underlying mechanism by which circRNA hsa-circ-000684 promotes the progression of gastric cancer (GC). Expression of hsa-circ-000684 and that of ZEB1 mRNA were elevated while microRNA-186 (miR-186) expression was downregulated in GC cell lines and clinical tissues. In addition, the effects of hsa-circ-000684 on the proliferation, migration, invasion, and tube formation of GC cells were examined through gain-and loss-of-function experiments. Furthermore, we introduced tumor xenografts into nude mice to better understand these effects in vivo. Either knockdown of hsa-circ-000684 or upregulation of miR-186 inhibited GC cell proliferation, migration, invasion, and tube formation in vitro, and reduced the xenograft tumor growth in nude mice. Moreover, we found that hsa-circ-000684 and ZEB1 directly bound to miR-186. Hsa-circ-000684 increased the expression of ZEB1 by binding to miR-186. The tumor suppressive effects of hsa-circ-000684 knockdown were reversed by inhibition of miR-186. Collectively, our data show that hsa-circ-000684 reduces the miR-186 expression which leads to an increase in the ZEB1 expression and, consequently, promotion of GC progression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oncogenes
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Neoplasias Gástricas
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MicroRNAs
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Homeobox 1 de Ligação a E-box em Dedo de Zinco
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RNA Circular
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article