Abstract
BackgroundMicroRNA (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.MethodsThe 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/β-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/β-catenin pathway-related proteins were also analysed.ResultsIn 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/β-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.ConclusionsIn summary, miR-200c overexpression inhibits proliferation of colon cancer targeting FUT4 to downregulate the Wnt/β-catenin pathway, which promises molecular targets to inhibit metastasis for colon cancer therapy.
Highlights
MicroRNA-200c has been widely reported to be involved in colon cancer progress
Low expression of miR-200c and high expression of fucosyltransferase 4 (FUT4) in colon cancer cells The mRNA expression of miR-200c and FUT4 in cells was measured by real-time quantitative polymerase chain reaction (RT-qPCR)
FUT4 is a target gene of miR-200c in colon cancer cells To determine whether FUT4 is a target gene of miR-200 in colon cancer cells, we performed target gene prediction between miR-200c and FUT4 using TargetScan software
Summary
MicroRNA (miR)-200c has been widely reported to be involved in colon cancer progress. This study aimed to investigate the mechanism of miR-200c targets fucosyltransferase 4 (FUT4) on the proliferation of colon cancer. A malignancy of the large intestine (colon), is a clinically highly malignant tumour of the digestive tract. Colon cancer ranks third in global gastrointestinal tumour incidence and fourth in mortality [1]. Colon cancer can cause blood in the stool, stomach pain, and changes in stool. If this disease is detected early, most patients with colon cancer can recover. There are more than one million new cases of colon cancer, and approximately 700,000 people die of colon cancer each year in 2013 globally [2]. The treatments for colon cancer are unsatisfactory
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