Abstract
ObjectiveThe aim of this study was to investigate the relationship of MACC-1 (metastasis-associated in colon cancer 1) and microRNA (miRNA) hsa-miR-574-5p and the function of hsa-miR-574-5p in colorectal cancer liver metastasis.MethodsLiver-metastatic nude mice model was constructed by injecting two human colorectal cancer cell lines (SW1116 and HCT116) labeled with green fluorescent protein (GFP) through spleen, and liver metastasis incidences were evaluated. We identified miRNAs that might regulate MACC-1 expression by bioinformatics analysis and further investigated the relationship of MACC-1 and hsa-miR-574-5p by luciferase reporter assay, quantitative RT-PCR and western blot. The effect of hsa-miR-574-5p on colony formation, cell invasion and cell spheroid formation was investigated by antisense transfected HCT116 cells and miRNA mimic transfected SW1116 cells.ResultsThe volume of liver metastasis induced by SW1116 cells (25.0 ± 4.4%) was significantly higher than that induced by HCT116 cells. Bioinformatics analysis showed hsa-miR-574-5p negatively regulated MACC-1 and then their interaction was demonstrated at mRNA and protein level. The direct relation between them was confirmed by luciferase reporter assay. And the knockdown of has-miR-574-5p demonstrated increased colony formation, cell invasion and cell spheroid formation in HCT116 cells, compared to control group (P < 0.05). Reverse results were obtained in mimic transfected SW1116 cells.ConclusionOur work firstly demonstrated that hsa-miR-574-5p negatively regulated MACC-1 expression in colorectal cancer cells. It was partly elucidated that hsa-miR-574-5p played a suppressive role in colorectal cancer liver metastasis by negatively directing MACC-1 expression, offering a novel therapeutic approach for colorectal cancer liver metastasis.
Highlights
Colorectal cancer liver metastasis is a bottleneck worldwide, which restricts patients from long-term survival
Bioinformatics analysis of miRNAs regulating Metastasis-associated in colon cancer 1 (MACC-1) expression The miRNAs that might regulate the MACC-1 gene expression was identified by bioinformatics analysis
Among those miRNAs, hsa-miR-574-5p expression level may be correlated to MACC-1 expression for the E value (0.10) was relatively lower
Summary
Colorectal cancer liver metastasis is a bottleneck worldwide, which restricts patients from long-term survival. There are about 500,000 cases of colorectal cancer liver metastasis every year [1]. The prognosis is often very poor [2]. The incidence of liver metastasis for colorectal cancer patients is still very high. More than 70% patients with liver metastasis cannot be surgically resected [2]. The 2-year recurrence rate is as high
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