Hsa-miR-574-5p negatively regulates MACC-1 expression to suppress colorectal cancer liver metastasis

Cancer Cell International

Zheng Wang¹  Jinxian Chen¹  Jian Tang¹  Zhe Cui¹ 

[1] Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

关键词: Liver metastasis;    miRNA;    MACC-1;    Colorectal cancer;   

Others  :  791909
DOI  :  10.1186/1475-2867-14-47

 received in 2013-10-23, accepted in 2014-05-22,  发布年份 2014

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2014 Cui et al.; licensee BioMed Central Ltd.

【 图 表 】

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