4.6 Article

MiR-200c/FUT4 axis prevents the proliferation of colon cancer cells by downregulating the Wnt/β-catenin pathway

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BMC CANCER
卷 21, 期 1, 页码 -

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BMC
DOI: 10.1186/s12885-020-07670-y

关键词

miR-200c; FUT4; Colon cancer; Wnt/beta-catenin pathway

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资金

  1. Natural Science Foundation Guidance Program of Liaoning Province [2019-ZD-0747]

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MiR-200c overexpression inhibits the proliferation of colon cancer cells by downregulating FUT4 and consequently suppressing the Wnt/β-catenin signaling pathway. In vivo experiments further confirmed the findings from the cell studies.
Background: MicroRNA (miR)-200c has been widely reported to be involved in colon cancer progress. However, the mechanisms of miR-200c in regulating tumor metastasis and growth remain to be fully elucidated. This study aimed to investigate the mechanism of miR-200c targets fucosyltransferase 4 (FUT4) on the proliferation of colon cancer. Methods: The miR-200c and FUT4 mRNA levels in LoVo and SW480 cells were measured by real-time quantitative polymerase chain reaction. Further, miR-200c mimic, FUT4 siRNA and FUT4 mimic were transfected into cells, separately. Cell counting kit-8, plate colony formation and transwell assays were used to analyse the cells biological behaviour.. Immunofluorescence was used to analyse the Ki-67 expression Moreover, the Wnt/beta-catenin pathway-related proteins were detected by western blots. A double luciferase experiment was performed to confirm the relationship between miR-200c and FUT4. In vivo, tumour growth and Wnt/beta-catenin pathway-related proteins were also analysed. Results: In vitro, the expression of miR-200c and FUT4 were negatively correlated in LoVo and SW480 cells (correlation coefficients were - 0.9046 and - 0.9236, respectively). MiR-200c overexpression inhibited the proliferation, migration and invasion of LoVo and SW480 cells by downregulating FUT4. The Ki67-positive cells and Wnt/beta-catenin signalling pathway-related proteins were reduced in the miR-200c overexpression and FUT4 silencing groups. A dual luciferase reporting system identified FUT4 as the target of miR-200c. The results in vivo were further confirmed the foundation of cells study. Conclusions: In summary, miR-200c overexpression inhibits proliferation of colon cancer targeting FUT4 to downregulate the Wnt/beta-catenin pathway, which promises molecular targets to inhibit metastasis for colon cancer therapy.

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