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MicroRNA-204 Inhibits the Growth and Motility of Colorectal Cancer Cells by Downregulation of CXCL8
Among all of the miRNAs, miR-204 has gained considerable attention in the field of cancer research. This study aimed to reveal the detailed functions and the underlying mechanism of miR-204 in colorectal cancer (CRC) cells. The expressions of miR-204 in CRC tumor tissues and cell lines were monitore...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cognizant Communication Corporation
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844723/ https://www.ncbi.nlm.nih.gov/pubmed/29402343 http://dx.doi.org/10.3727/096504018X15172747209020 |
Sumario: | Among all of the miRNAs, miR-204 has gained considerable attention in the field of cancer research. This study aimed to reveal the detailed functions and the underlying mechanism of miR-204 in colorectal cancer (CRC) cells. The expressions of miR-204 in CRC tumor tissues and cell lines were monitored. Expressions of miR-204 and CXCL8 in Caco-2 and HT-29 cells were altered by transfection, and then cell viability, apoptosis, migration, invasion, EMT-related protein expression, and PI3K/AKT/mTOR pathway protein expression were assessed. We found that miR-204 was expressed at low levels in CRC tumor tissues and cell lines when compared to their normal controls. miR-204 overexpression reduced the viability, migration, and invasion of Caco-2 and HT-29 cells while significantly inducing apoptosis. miR-204 overexpression upregulated E-cadherin expression and downregulated N-cadherin and vimentin expressions. CXCL8 was a target of miR-204, and miR-204 suppression could not increase cell viability, migration, invasion, and EMT procedure when CXCL8 was silenced. Moreover, miR-204 overexpression decreased the phosphorylated levels of PI3K, AKT, and mTOR. The increased phosphorylations of PI3K, AKT, and mTOR, and the upregulation of CXCL8 induced by miR-204 suppression were all abolished by the addition of LY294002 and AZD8055 (inhibitors of PI3K/AKT and mTOR, respectively). To conclude, we demonstrated a tumor-suppressive miRNA in CRC cell lines, miR-204, which is poorly expressed in CRC tissues and cell lines. miR-204 exerted antigrowth, antimigration, anti-invasion, and anti-EMT activities, which might be via deactivating the PI3K/AKT/mTOR pathway and repressing CXCL8 expression. |
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