title: Hsa-miR-574-5p negatively regulates MACC-1 expression to suppress colorectal cancer liver metastasis.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  Liver-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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jinxian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
keywords: Colorectal cancer; Liver metastasis; MACC-1; miRNA